bluuebunny/crossref_metadata_2025 huggingface dataset:
SEA‐URCHIN SPERMATOZOA
Authors: ROTHSCHILD LORD
Published: January 2008

i. The head of the sea‐urchin spermatozoon is pear‐shaped and axially symmetrical. The sub‐microscopic morphology of the middle piece has not been investigated, but the tail, which terminates in an axial fibre, probably contains spiral or coiled structures, as in mammalian spermatozoa.

2. Spermatozoa of Psammechinus miliaris swim in spirals (frequency, 30–40 per sec), at an average translatory speed of 200/x/sec. at 18o C. This figure applies to very dilute suspensions. The spermatozoa of Echinus esculentus do not always swim in spirals.

3. The evidence in favour of sea‐urchin spermatozoa being attracted by egg secretions is not conclusive. Experiments to settle this controversial question could be done without great difficulty.

4. Little is known about the metabolism of sea‐urchin spermatozoa. The most important features are:

(a)No movement in absence of oxygen.

(b)Negligible acid production in presence or absence of oxygen.

(c)Over certain limits, oxygen consumption per spermatozoon an inverse function of sperm concentration.

(d)Cytochromes a, b, c, e and a3, succinic dehydrogenase, cocarboxylase, and catalase (in significant quantities) present.

(e)Endogenous substrate unknown, though possibly carbohydrate.

(f) Respiration inhibited by cyanide, and photo‐reversibly by carbon monoxide.

A large number of substances, of widely different types, are said to stimulate or maintain the oxygen consumption of semen or spermatozoa. Among these are succinate, malonate, iodoacetate, copper, zinc, calcium, albumin and seminal plasma. The mode of action of these substances is in general obscure.

5. Sea‐urchin spermatozoa contain a proteolytic enzyme which decreases the viscosity of gelatine, and desoxyribonuclease.

6. Sea‐urchin spermatozoa contain or secrete three substances with characteristic chemical and biological properties. These substances and their principal characteristics are:

(a)Androgamone I. Not a protein. Inhibits sperm movement in certain circumstances.

(b)Androgamone II. Protein. Dissolves or precipitates egg jelly. Also called Antifertilizin.

(c)Androgamone III. Not a protein. Liquefies egg cortex. Sometimes called Sperm Lysin.

7. The spontaneously reversible agglutination of sea‐urchin spermatozoa in the presence of egg secretions, and in particular of Gynogamone II, has a number of characteristics in common with serological reactions. In recent years this subject has been extensively studied and reviewed by Tyler (1948). Some of the more important conclusions are:

(a)Spermatozoa and G. II are multivalent with respect to their complementary combining groups, a condition which is responsible for the agglutination of spermatozoa in G. II.

(b)Multivalent G. II can be converted into a univalent form in which it reacts with homologous spermatozoa, but without causing agglutination.

(c)The sperm‐G. II reaction exhibits the zone phenomenon (maximum agglutination when the two reactants are present in particular proportions).

(d)The sperm‐G. II reaction causes a reduction in the fertilizing capacity of agglutinated spermatozoa.
EVALUATION OF THE SELECTIVITY OF α‐ADRENORECEPTOR BLOCKING DRUGS FOR POSTSYNAPTIC α1‐ AND α2‐ADRENORECEPTORS IN A SIMPLE ANIMAL MODEL
Authors: TIMMERMANS P. B. M. W. M. , VAN MEEL J. C. A. , VAN ZWIETEN P. A.
Published: January 2008

The increase in diastolic pressure of pithed, normotensive rats was determined after i.v. administration of the α‐adrenoreceptor agonists L‐phenylephrine and B‐HT 933.

α‐Adrenoreceptor antagonists varied widely in their relative inhibitory effects towards either L‐phenylephrine‐ or B‐HT 933‐induced vasoconstrictor responses. Prazosin displayed the highest affinity for the postsynaptic α‐adrenoreceptor triggered by L‐phenylephrine. The rank order of potency was further: phentolamine > dihydroergotamine > clozapine > corynanthine > azapetine > yohimbine > piperoxan > tolazoline > mianserin > rauwolscine. On the other hand, the rank order of potency towards B‐HT 933 was: dihydroergotamine > rauwolscine > yohimbine > phentolamine > piperoxan > prazosin > tolazoline > mianserin > corynanthine > azapetine > clozapine. These data are in general agreement with the classification for α1‐(triggered by L‐phenylephrine) and α2‐(triggered by B‐HT 933) adrenoreceptors. Both populations are present postsynaptically in vascular smooth muscle of the pithed rat and are involved in vasoconstriction.

The ratio of KB post α2/KB post α1 was calculated as a measure of selectivity for either α‐adrenoreceptor site. The α‐adrenoreceptor antagonists used cover a 20,000‐fold range of activity ratios. The antagonists most selective for either type were prazosin (α1) and rauwolscine (α2). The selectivity of the α‐adrenoreceptor antagonists for postsynaptic α1‐ and α2‐adrenoreceptors in the intact circulatory system of the pithed rat is comparable with the reported selectivity of these blocking agents for α1 (postsynaptic)‐ and α2 (presynaptic)‐adrenoreceptors in the rabbit isolated pulmonary artery.

It is concluded that two distinct types of postsynaptic α‐adrenoreceptors participate in vasoconstriction in the pithed rat. Apart from the classical α1‐adrenoreceptor, vascular smooth muscle of the pithed rat contains postsynaptic α2‐adrenoreceptors resembling those previously found mainly presynaptically. The presence of separate classes of postsynaptic α1‐ and α2‐adrenoreceptors in the intact circulatory system of the pithed rat offers the possibility to use this relatively simple animal model as an in vivo test system for the pharmacological characterization of α‐adrenoreceptor agonists and antagonists.
ADRENORECEPTORS IN THE HUMAN PENIS
Authors: ADAIKAN P. G. , KARIM S. M. M.
Published: January 2008

Adrenaline, noradrenaline and phenylephrine caused contraction of the corpus cavernosum muscle of the human penis. These sympathomimetic amines did not produce inhibitory effects even in the presence of the α‐adrenoreceptor blocker, phentolamine. The effect of dopamine was similar to that produced by these three sympathomimetic amines. Higher doses of isoprenaline and salbutamol also contracted this preparation.

Cocaine and guanethidine enhanced the motor response to adrenaline, noradrenaline and phenylephrine while the action of dopamine was blocked by these two drugs.

The motor response to adrenaline, noradrenaline and phenylephrine was antagonized by phentolamine and often potentiated by the β‐adrenoreceptor blocking drug, propranolol. The contractions produced by high doses of salbutamol and isoprenaline were also abolished by phentolamine. These findings indicate that the motor response to sympathomimetic amines is the result of activation of α‐adrenoreceptors in the corpus cavernosum muscle.

At low doses, isoprenaline and salbutamol relaxed the corpus cavernosum muscle strip. The inhibitory action was blocked by low concentrations of the β‐adrenoreceptor antagonist, propranolol but not by practolol (β1‐adrenoreceptor antagonist) and butoxamine (β2‐adrenoreceptor antagonist). β‐adrenorecepcors are present in the corpus cavernosum muscle but these are unlikely to be either of the β1 or β2 type. The possible existence of a third type of β‐adrenoreceptor is suggested.
METABOLISM AND PRESYNAPTIC INHIBITORY EFFECTS OF ADENOSINE IN RAT VAS DEFERENS
Authors: WILLEMOT JOAN , PATON DAVID M.
Published: January 2008

In the rat vas deferens, adenosine caused rapid presynaptic inhibition of the twitch response stimulated at 0.2 Hz, this effect being maximal within 30 sec. The metabolism of [14C]adenosine was examined under these conditions. For 2–40juM adenosine and for incubations up to 120 sec, deamination of adenosine was quantitatively greater than incorporation into adenine ribonucleotides.

Exposure of tissues to 2juM deoxycoformycin reduced deamination of 10juM [14C]adenosine by about 90%, but did not alter the presynaptic inhibitory action of adenosine. Exposure of tissues to 1juM hydroxy‐nitrobenzylthioguanosine, an adenosine uptake inhibitor, reduced the incorporation of 2–40juM [14C]‐adenosine into adenine ribonucleotides by 25–39% and potentiated the presynaptic inhibitory action of adenosine by 46–105%.

Postganglionic sympathetic denervation of the tissue did not alter the metabolism of [14C]adenosine, indicating that the metabolism observed occurred almost exclusively in smooth muscle.

It is concluded that the concentration of adenosine in the immediate vicinity of the presynaptic adenosine receptor is not greatly affected by deamination but is influenced by adenosine uptake. It is also possible that hydroxynitrobenzylthioguanosine may modify the affinity or intrinsic activity of the presynaptic adenosine receptor.
RESPONSES OF THE ISOLATED ANOCOCCYGEUS MUSCLE OF THE MOUSE TO DRUGS AND TO FIELD STIMULATION
Authors: GIBSON A. , WEDMORE CAROLINE V.
Published: January 2008

The responses of the isolated anococcygeus muscle of the mouse to drugs and to field stimulation were investigated.

Fluorescence micrographs of transverse sections of the muscle revealed fluorescent nerve fibres in control tissues, but not in tissues from mice pretreated with 6‐hydroxydopamine.

The isolated muscle displayed no spontaneous tone or rhythmic activity. Field stimulation produced frequency dependent contractions which were blocked by phentolamine and by low concentrations of guanethidine (500 nM). Higher concentrations of guanethidine (30 juM) raised muscle tone and, subsequently, field stimulation produced frequency dependent relaxations. In muscles from 6‐hydroxydopamine pretreated mice neither field stimulation nor guanethidine produced contractions, but when muscle tone was raised by carbachol inhibitory responses to field stimulation were still observed.

Contractions of the muscle were produced by noradrenaline (α‐adrenoreceptors), acetylcholine (muscarinic receptors), 5‐hydroxytryptamine, and prostaglandins E1, E2, and F2a.

Adenosine 5′‐triphosphate (ATP) normally produced muscle contraction, but following incubation of the tissue with indomethacin, ATP produced relaxations of carbachol‐induced tone.

Vasoactive intestinal polypeptide, but not bradykinin, produced relaxations of tissues in which tone had been raised by carbachol.

The isolated anococcygeus muscle of the mouse provides a useful preparation for the study of various aspects of autonomic neurotransmission in smooth muscle.
EFFECT OF THYROID STATUS ON β‐ADRENORECEPTORS AND MUSCARINIC RECEPTORS IN THE RAT LUNG
Authors: BAKER S. P.
Published: January 2008

The effects of thyroid status on the specific binding of the muscarinic ligand (–)‐[3H] quinuclidinyl benzilate (QNB) and of the β‐adrenoreceptor ligand (–)‐[3H] dihydroalprenolol (DHA) in the adult rat lung were investigated.

The specific binding of (–)‐[3H] quinuclidinyl benzilate (QNB) to lung membranes was saturable and the equilibrium dissociation constant (KD) determined from Scatchard analysis was 54 pM. Kinetic analysis of the binding of [3H] QNB yielded a KD of 42 pM. [3H] QNB binding was inhibited by muscarinic agonists and antagonists, the order of their potency was l‐hyoscyamine>atropine>scopolamine>oxotremorine>carbachol. These data were consistent with [3H] QNB binding to the muscarinic receptor.

Adult male rats treated for 2 weeks with the antithyroid agent 3‐amino‐1,2,4‐triazole (ATZ) showed a 52% and 80% reduction in the serum concentration of triiodothyronine (T3) and thyroxine (T4) respectively. These hypothyroid rats also had a 39% decrease in the concentration of lung β‐adrenoreceptors and a 37% decrease in the concentration of lung muscarinic receptors as compared to euthyroid controls. Concurrent treatment of rats with ATZ and T4 for 2 weeks resulted in a reduction of 15% and 20% in the concentration of lung β‐adrenoreceptors and muscarinic receptors respectively. The KD values for [3H] DHA and [3H] QNB binding did not change with the ATZ or ATZ + T4 treated groups.

Administration of T4 (500 μg/kg/day) to male rats for 12 days did not result in any significant change in the concentration of either β‐adrenoreceptors or muscarinic receptors compared to euthyroid controls. No change in the KK values for [3H] DHA or [3H] QNB binding were detected.

The results show that hypothyroid rats have a reduced lung concentration of both β‐adrenoreceptors and muscarinic receptors whereas in hyperthyroid rats these receptors do not significantly change from euthyroid controls.
STRUCTURE‐ACTIVITY RELATIONS FOR PRESYNAPTIC INHIBITION OF NORADRENERGIC AND CHOLINERGIC TRANSMISSION BY ADENOSINE: EVIDENCE FOR ACTION ON A1 RECEPTORS
Authors: PATON D. M.
Published: January 2008

This study was designed to determine the structure‐activity relations for presynaptic inhibition by adenosine of noradrenergic transmission in rat vas deferens and of cholinergic transmission in guinea‐pig ileum.

The mid‐portion of vasa deferentia and segments of ileum were continuously stimulated at 0.2 Hz and the IC50 values of adenosine analogues for inhibition of the twitch responses determined.

In both tissues, loss of the 2’and/or 3’hydroxyl groups resulted in a very marked loss of activity, whereas substitution at the 5’position was compatible with considerable activity.

In both tissues, an amino group at C6 on the purine moiety was essential for activity. Halide substitutions at the C2 position and bulky substitutions at the N6 position were compatible with increased activity.

The L‐diastereomer of N6‐phenylisopropyladenosine was approximately 100 times more potent than the D‐diastereomer in both tissues.

It was concluded that adenosine acts at presynaptic receptors with ‘R’ site characteristics to inhibit noradrenergic and cholinergic transmission and further that these receptors may belong to the A1 subtype.
THE EFFECTS OF INTRAVENOUS 6‐HYDROXYDOPAMINE ON PERIPHERAL α‐ADRENORECEPTORS
Authors: HAMILTON C. A. , REID J. L.
Published: January 2008

Peripheral α‐adrenoreceptor‐mediated responses were studied in conscious intact rabbits and in animals pretreated with intravenous 6‐hydroxydopamine (50 mg/kg).

Treatment caused a large decrease in noradrenaline in plasma and peripheral tissue but only small falls in blood pressure.

There was a shift to the left in pressor dose‐response curves to the α‐adrenoreceptor agonist phenylephrine and the mixed α1/α2‐adrenoreceptor agonist noradrenaline in 6‐hydroxydopamine‐pretreated animals. The α1‐adrenoreceptor antagonist prazosin was less effective at blocking the phenylephrine pressor response in these animals.

There was no change in pressor responses to the α2‐adrenoreceptor selective agonists clonidine and guanabenz and α‐adrenoreceptor antagonists were equally effective at blocking this pressor response in 6‐hydroxydopamine‐pretreated and in intact rabbits.

In conscious animals 6‐hydroxydopamine pretreatment causes alteration in responses mediated by postsynaptic α1‐but not postsynaptic α2‐adrenoreceptors. These changes may help maintain blood pressure in the 6‐hydroxydopamine treated rabbits.
MODULATION OF ENDOGENOUS NORADRENALINE RELEASE BY PREJUNCTIONAL α‐ADRENORECEPTORS: COMPARISON OF A CEREBRAL AND PERIPHERAL ARTERY
Authors: DUCKLES SUE PIPER
Published: January 2008

Stimulation‐evoked fractional release/pulse of noradrenaline (NA) is markedly different in the rabbit basilar artery as compared to the rabbit ear artery. Therefore, using both agonists and antagonists of prejunctional α‐adrenoreceptors, the hypothesis that there are differences in prejunctional mechanisms between these functionally different arteries was tested.

Clonidine (10−6M) had similar effects on NA release in both vessels, decreasing release at 2 Hz, but increasing release at 8 Hz. However, 10−5M clonidine had different effects in the two vessels.

α‐Adrenoreceptor antagonists, phentolamine (10−6M), yohimbine (10−5M), and phenoxybenzamine (10−5M), all increased NA release to a similar extent in both vessels. However, the effect of phenoxybenzamine was considerably greater than that of the other two antagonists, suggesting that it may have additional sites of action.

When the effects of modest drug concentrations were considered, no major qualitative or quantitative differences in the effects of agonists and antagonists on NA release from the two vessels were seen. Thus, the difference in fractional NA release between the basilar and ear arteries cannot be accounted for by differences in prejunctional α‐adrenoreceptor modulation.
THE INOTROPIC AND CHRONOTROPIC EFFECTS OF PHYSOSTIGMINE AND NEOSTIGMINE ON GUINEA‐PIG ISOLATED ATRIA
Authors: DE WILDT D. J. , OUD P. H. J. H. , PORSIUS A. J.
Published: January 2008

Physostigmine (0.1‐1 mM) induced dose‐dependent negative and neostigmine (0.1–1 mM) positive inotropic effects on driven guinea‐pig isolated atria. Physostigmine decreased and neostigmine increased cardiac frequency of spontaneously beating atria.

The depression of amplitude of contraction by physostigmine cannot be attributed to its inhibitory effect on tissue cholinesterase. The negative inotropic action of physostigmine is not influenced by preincubation with atropine.

The positive inotropic effect of neostigmine is not caused by a nicotine‐like action of the drug. Neostigmine (1 mM) counteracts the negative inotropic effect of acetylcholine. The possible mechanisms of action are discussed.
AN EXAMINATION OF AUTONOMIC NERVOUS FUNCTION IN GENETICALLY DIABETIC MICE
Authors: WILSON HILARY F. , MAYER J. HEIDI , CLARKE SHARON A. , TOMLINSON D. R.
Published: January 2008

1 This study was designed to determine whether the autonomic innervation of the heart and vas deferens in genetically diabetic mice exhibited dysfunction similar to those seen in chemically diabetic animals and diabetic patients.

2 Diabetic mutant mice (outcrossed from the C57 BL/KS db/db strain) were compared with their non‐diabetic litter‐mates at age 20 to 22 weeks. Right and left atria and vasa deferentia were removed from freshly killed animals and subjected to nerve stimulation and treatment with noradrenaline (NA) or acetyl‐choline (ACh) in organ baths.

3 Right atria from diabetic animals were less responsive to noradrenergic nerve stimulation than control preparations but there was no such difference between the noradrenergic responses of left atria from the two groups of mice. Both atria were hypersensitive to exogenous NA.

4 Atria from diabetic mice responded to cholinergic nerve stimulation and exogenous ACh in a fashion similar to those of non‐diabetic mice. Likewise the responses of vasa deferentia to nerve stimulation were similar in the two groups. These findings are indicative of some autonomic nervous dysfunction characteristic, to an extent, of diabetes mellitus.
CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β2‐MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT
Authors: LOTTI V. J. , CERINO D. , KLING P.
Published: January 2008

1 Low concentrations of isoprenaline (EC50= 45.6 nM) inhibited contractions in the isolated field stimulated rat vas deferens. This inhibitory effect was markedly attenuated by the postjunctional β2‐adreno‐receptor antagonist timolol, but not affected by the prejunctional α2 or postjunctional α1‐adrenoreceptor antagonists rauwolscine and prazosin, respectively.

2 In vas deferens of rats previously treated with reserpine, the postjunctional β2‐adrenoreceptor‐mediated inhibitory response to isoprenaline was markedly potentiated.

3 High concentrations of isoprenaline (EC50= 1.5 uM) also inhibited contractility in tissues in which postjunctional β2‐adrenoreceptors were maximally blocked by high concentrations of timolol. This contractile inhibition produced by isoprenaline was abolished by rauwolscine but not significantly altered by prazosin or pretreatment of the rats with reserpine indicating stimulation of prejunctional α2‐adreno‐receptors.

4 Rauwolscine pretreatment unmasked an ability of isoprenaline (EC50= 17.1 juM) to produce enhancement of field stimulation‐induced contractions. This response was abolished by prazosin but was unaffected by timolol or reserpinization indicating an action upon postjunctional α1‐adrenoreceptors.

5 The data indicate isoprenaline activates adrenoreceptor mechanisms in the field stimulated rat vas deferens by a direct action not dependent upon endogenous catecholamines and with an order of activity of β2>α2>α1. Pretreatment with reserpine produces rapid and selective development of supersensitivity to the postjunctional β2‐mediated inhibitory response of isoprenaline in this preparation.
THE EFFECTS OF 6‐HYDROXYDOPAMINE OR (–)‐NORADRENALINE TREATMENT IN VITRO ON NORADRENERGIC TRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: DOGGRELL SHEILA A. , WALDRON J. B.
Published: January 2008

The effects of 6‐hydroxydopamine treatment in vitro for varying times on the overflow of 3H (following preloading of the tissue with (–)‐[3H]‐noradrenaline) and the accumulation of 3H from (–)‐[3H]‐noradrenaline have been investigated in the rat anococcygeus muscle. In addition the effects on contractile responses to field stimulation and to other stimulants are reported.

Following preloading of the rat anococcygeus muscle with 5 times 10‐7M (–)‐[3H]‐noradrenaline for 1 h, the overflow of 3H was increased by 6‐hydroxydopamine (1 times 10–3M). At the end of the overflow period the tissue content of 3H was reduced by 95% from tissues treated with 6‐hydroxydopamine for ≥ 30 min. The rat anococcygeus muscle accumulated 3H from a medium containing 5 times 10–8M (–)‐[3H]‐noradrenaline. The ability to accumulate 3H was reduced after incubation in 6‐hydroxydopamine for 5 min and abolished by longer incubations. These effects of 6‐hydroxydopamine probably represent depletion of endogenous (–)‐noradrenaline stores and destruction of noradrenergic neurones.

6‐Hydroxydopamine induced contractions of the rat anococcygeus that were abolished by phentolamine (1 times 10‐6M).

The excitatory contractile responses to field stimulation were reduced after exposure to 6‐hydroxy‐dopamine for 5 min and were abolished after longer exposures. 6‐Hydroxydopamine had no effect on the inhibitory response to field stimulation. The contractile responses to (–)‐noradrenaline were potentiated after 6‐hydroxydopamine.

Following 6‐hydroxydopamine treatment for 5 min the responses to tyramine were potentiated. This potentiation was probably due to the release of endogenous (–)‐noradrenaline. The responses to tyramine were reduced after longer treatments (30–120 min).

Short incubations of the anococcygeus muscle with 6‐hydroxydopamine or (–)‐noradrenaline had no effect on the subsequent responses to acetylcholine whereas after a 180 min treatment the responses were reduced. This effect was possibly due to fatigue of the muscle. Incubations with (–)‐noradrenaline for 60 min had no effect on the responses to field stimulation or to (–)‐noradrenaline. After longer pretreatments the responses were reduced. Thus after long exposures to (–)‐noradrenaline, and probably to 6‐hydroxy‐dopamine, responses may be reduced by fatigue or by desensitization at α‐adrenoreceptors.

7 These results suggest that, in the rat anococcygeus muscle, a selective abolition of noradrenergic transmission was obtained by treating the tissue with 6‐hydroxydopamine for 30–60 min. The contractile responses to tyramine in this tissue may, in part, be due to a direct postjunctional action.
Reassessment of the blocking activity of prazosin at low and high concentrations on sympathetic neurotransmission in the isolated mesenteric vasculature of rats
Authors: Yamamoto R. , Cline W. H. , Takasaki K.
Published: January 2008

1 The overflow of endogenous noradrenaline from the rat mesenteric arterial vasculature was determined along with the perfusion pressure response to periarterial nerve stimulation (PNS) (4–12 Hz).

2 The PNS‐induced pressor responses were blocked by prazosin at 3x 108 M but not by prazosin at 10−6 M or the combination of prazosin at 3 × 10−8 M and yohimbine (10−7 M).

3 The PNS‐induced overflow of endogenous noradrenaline was significantly augmented by prazosin at 10−6 M or the combination of prazosin at 3 × 10−8 M and yohimbine (10−7 M) but not by prazosin at 3 × 10−8 M alone.

4 The PNS‐induced pressor response and endogenous noradrenaline overflow, in the absence of prazosin, were not significantly influenced by α, β‐methylene‐adenosine triphosphate (α, β‐methylene ATP) (3x10−6 M). The pressor responses to PNS which remained after prazosin at 10−6 M were abolished by pretreatment with α, β‐methylene ATP and therefore attributable to coreleased ATP.

5 The pressor responses to exogenous noradrenaline were abolished by prazosin at both 3 × 10−8 M and 10−6 M.

6 These results suggest that no functionally significant amount of ATP was coreleased with noradrenaline by PNS in the presence of prazosin at low concentrations which blocked only postjunctional α1‐adrenoreceptors.

7 Thus, these results indicate that the effects of prazosin at high concentrations, such as 10−6 M, on sympathetic neurotransmission should not be ignored when considering the mechanisms of vasoconstrictor responses to PNS following high concentrations of prazosin.
Prostaglandin I2 and thromboxane A2production in relation to α1 and α2‐adrenoreceptor activation in the normotensive and hypertensive rat
Authors: Pipili E. , Zoumboulis G. , Maragoudakis M. E.
Published: January 2008

1 The perfused mesenteric arterial bed (MAB) from normotensive (WKY) and hypertensive (SHR) rats was used as a model to investigate the relationship between α1 and α2‐adrenoreceptor activation and prostanoid release.

2 Prostaglandin I2 (PGI2) and small amounts of thromboxane A2 (TXA2) are released from this preparation and can be monitored in the perfusate under basal and stimulated conditions.

3 Noradrenaline (NA) caused a significant increase in the release of PGI2 from the MAB of both WKY and SHR. Both basal and NA‐stimulated PGI2 release were lower in the SHR, whereas pressor responses to NA were higher. Noradrenaline caused a very small increase in TXA2 release in the WKY only and the basal release of this prostanoid was again lower in the SHR.

4 Prazosin, an α1‐selective antagonist (10−10, 10−9, 10−8M) was more effective in blocking pressor responses to NA in the SHR than in the WKY, did not affect the NA‐induced release of PGI2 in either group and abolished the small increase of TXA2 release in WKY.

5 Rauwolscine, an α2‐selective antagonist (10−8, 10−7, 10−6 M) was more effective in reducing pressor responses to NA in the SHR than in the WKY. It abolished, from 10−7M upwards, the NA‐induced release of PGI2 in the WKY and reduced it in the SHR. The NA‐induced release of TXA2 was abolished in WKY.

6 The observed differences in the effects of rauwolscine and prazosin do not correlate with the effects of these antagonists on pressor responses since both reduce the latter but only rauwolscine abolishes the stimulated PGI2 release.

7 These results indicate that in the SHR, the mechanisms mediating the release of PGI2 from the MAB may be similar but not identical to those in the WKY. The observation that an increase in adrenergically induced pressor responses is not followed by an increase in PGI2 release, which is in fact reduced in the SHR, suggests a more complex regulation of this relationship which may have pathophysiological implications.
Differential regulation of cardiac α‐ and β‐adrenoceptors by the sympathetic nervous system
Authors: Chess‐Williams Russell , Doubleday Bridget , Reynolds Gavin P.
Published: January 2008

1 The effects of depressed sympathetic function on the inotropic responses of the heart to sympathomimetic amines have been examined in rats immunized against nerve growth factor (NGF) 6 weeks prior to the isolation of cardiac tissues.

2 The activity of tyrosine hydroxylase in cervical sympathetic ganglia and the levels of noradrenaline in ventricular tissue were significantly reduced in NGF‐immunized rats.

3 Left atria and papillary muscles from NGF‐immunized rats were supersensitive to the β‐adrenoceptor agonist isoprenaline when compared with controls.

4 The responses of cardiac tissues to the α‐adrenoceptor agonist phenylephrine were unaffected by immunization.

5 These results support the hypothesis that cardiac β‐ but not α‐adrenoceptor sensitivity is regulated by the sympathetic nervous system.
Spectral analysis of blood pressure and heart rate variability in response to stress from air‐jet in the Lyon rat
Authors: Blanc Jocelyne , Grichois Marie‐Laure , Vincent Madeleine , Elghozi Jean‐Luc
Published: January 2008

1 Power spectral analysis of the frequency of wave‐forms of blood pressure and heart rate was used to characterize short‐term fluctuations of these parameters in three strains of conscious Lyon rat, normotensive (LL and LN) and hypertensive LH.

2 A mild stress produced by means of a jet of air elicited blood pressure rises, associated with tachycardia. This response was of similar magnitude in the three strains. The stressor amplified the medium frequency (195–605 mHz) Mayer waves of blood pressure and heart rate which are under autonomic control.

3 Clonidine (10 μg kg−1 i.v.) lowered blood pressure and heart rate and dramatically reduced the amplitude of blood pressure and heart rate oscillations in the frequency region of 195–605 mHz.

4 A jet of air applied after clonidine administration led to blood pressure rise associated with tachycardia and enhanced oscillations in the 195–605 mHz region.

5 These results indicate that in Lyon normotensive and hypertensive rats, a mild emotional stressor elicits blood pressure and heart rate rises associated with spectral modifications reflecting sympathetic hyperactivity. Clonidine lowers blood pressure and heart rate and reduces their related variabilities. This effect is more pronounced in LH rats than in their normotensive controls. Clonidine appears to reduce the autonomic response to stress as indicated by the medium frequency oscillations.
Opiate and opiate antidiarrhoeal drug action on rat isolated intestine
Authors: Coupar I. M. , Luca A. De
Published: January 2008

1 Stimulation of segments of rat jejunum (2.5, 5, 10, 20 and 40 Hz for 8 s) and ileum (10 Hz) resulted in a fast atropine‐sensitive contraction during stimulation and a non‐cholinergic after‐contraction. Stimulation of segments with single pulses at 0.1 Hz had no effect. The colon (10 Hz) usually responded only with single large atropine‐sensitive contractions.

2 The responses of the jejunum (2.5–40 Hz, 8 s) were unaffected by the μ‐receptor ligands morphine (0.3 μM) and RX 783006 (0.3 μM) or the k‐receptor ligand, ethylketocyclazocine (0.3 μM). The cholinergic contraction of the colon was unaffected by ethylketocycazocine (0.3 μM), but was reduced slightly by morphine at high concentrations only.

3 The prototype δ‐opiate receptor ligand D‐Ala2‐D‐Leu5‐enkephalin (DADLE; 30 nM) reduced the contraction during stimulation (2.5, 5, 10 and 20 Hz for 8 s) of the rat jejunum. The IC50 value for inhibition of the contraction elicited by stimulation at 10 Hz was 3.2 in the jejunum and was 12 nM in the ileum. Contractions of the colon were only slightly inhibited at a high concentration of DADLE (1 μM).

4 DADLE had no effect on contractions elicited by acetylcholine, at a concentration of up to 3 μM in segments of jejunum. Naloxone (1 μM) abolished the inhibitory effect of DADLE on the cholinergic contraction of the electrically stimulated jejunum. In addition, naloxone caused a large enhancement of control responses to stimulation.

5 Only high concentrations of the antidiarrhoeals loperamide and diphenoxylate inhibited the contraction elicited at 10 Hz in the jejunum (IC50, 1.3 and 7.1 μM, respectively) and ileum (loperamide IC50, 0.5 μM). The same concentrations of these drugs also inhibited the effect of exogenously added acetylcholine. A similar pattern of findings was made in the colon.

6 The results show marked differences in responses to transmural stimulation and to opiate drugs compared to those previously obtained from guinea‐pig ileum. Furthermore, it appears from the results that the cholinergic nerves of the rat jejunum and ileum possess non‐μ, non‐k, enkephalin‐sensitive opiate receptors, which upon stimulation reduce the amount of depolarization‐induced acetylcholine release. Finally, the opiate antidiarrhoeals appear to act postsynaptically.
Prejunctional effects of cromakalim, nicorandil and pinacidil on noradrenergic transmission in rat isolated mesenteric artery
Authors: Fabiani Maurizio E. , Story David F.
Published: January 2008

1 The present study investigated the effects of cromakalim, nicorandil and pinacidil on resting and stimulation‐induced (S‐I) effluxes of radioactivity from rat isolated mesenteric artery preparations in which the noradrenergic transmitter stores had been radiolabelled with [3H]‐noradrenaline. The efflux of radioactivity evoked by field stimulation of peri‐arterial sympathetic nerves (pulses at 2 Hz frequency in trains of 60 s duration) was taken as an index of transmitter noradrenaline release.

2 Cromakalim (1–100 μm) and nicroandil (1–1000 μm) produced minor effects on resting and S‐I effluxes of radioactivity, but these did not exhibit concentration‐dependency.

3 Pinacidil (1–1000 μm) produced concentration‐dependent increases, in both resting and S‐I effluxes of radioactivity. With 1000 μm pinacidil, resting and S‐I effluxes were increased to approximately 348% and 358% of their respective control values.

4 The effects of pinacidil on resting and S‐I effluxes were unaltered when the neuronal amine transport system was inhibited by desipramine (1 μm).

5 Inhibition of monoamine oxidase with pargyline (100μm) treatment markedly reduced the enhancement of resting efflux by 1000 μm pinacidil but did not alter its effect on S‐I efflux. It is proposed that the enhanced resting efflux produced by pinacidil without pargyline treatment consists of deaminated [3H]‐noradrenaline metabolites formed from [3H]‐noradrenaline displaced from transmitter storage vesicles by pinacidil.

6 The enhancement of S‐I efflux by pinacidil does not appear to involve disruption of α2‐adrenoceptor auto‐inhibition of transmitter release since equi‐effective concentrations of phentolamine (1 μm) and pinacidil (1000 μm) produced additive effects on S‐I efflux, whereas increasing the concentration of phentolamine from 1 to 2m produced no further increases in S‐I efflux.

7 In conclusion this, study has provided no evidence of a prejunctional inhibitory effect of the potassium channel openers cromakalim, nicorandil and pinacidil on transmitter noradrenaline release. However, the findings with pinacidil suggest that, in high concentrations, pinacidil displaces noradrenaline from transmitter stores, such that deaminated noradrenaline metabolites are released from the nerve terminals. Furthermore, pinacidil enhances S‐I transmitter noradrenaline release, possibly by blocking neuronal potassium channels.
The β‐adrenoceptor selectivity profile of BRL 37344 in the pithed rat
Authors: Oriowo M. A. , Sennitt M. V. , Smith S. A. , Ruffolo R. R. , Cawthorne M. A.
Published: January 2008

1 Rats were pithed in order to srupt baroreflex pathways. Heart rate was used as a measure of β1‐adrenoceptor activity, blood pressure as a measure of β2‐adrenoceptor activity and oxygen consumption and brown adipose tissue temperature as measures of β3‐adrenoceptor activity.

2 The effects of the selective β3‐adrenoceptor agonist BRL 37344 were compared with those of isoprenaline, a non‐selective β ‐adrenoceptor agonist, and denopamine and salbutamol, which are respectively β1 and β2‐adrenoceptor agonists.

3 Denopamine was 10‐fold more potent on heart rate than blood pressure, whilst salbutamol was 18‐fold more potent on blood pressure than heart rate. These findings confirm that in this preparation increases in heart rate are predominantly β1‐adrenoceptor‐mediated, whilst blood pressure is β2‐adrenoceptor‐mediated. Further confirmation is provided by the blockade with atenolol, of the chronotropic effect, but not the blood pressure effect, of isoprenaline.

4 BRL 37344 was the most potent β ‐adrenoceptor agonist on both oxygen consumption and brown adipose tissue temperature, revealing the β3‐nature of these responses. Dose‐response curves for oxygen consumption and brown adipose tissue temperature were identical, whichever of the β ‐adrenoceptor agonists was used. Both systems may be considered equally effective as indicators of β3‐adrenoceptor agonist activity.
Loss of dopamine D1‐like receptors in the umbilical artery of pre‐eclamptic subjects
Authors: De Almeida José Antonio Ferreira , Cavallotti Carlo , Leite Luis Pereira , Ricci Alberto , Zaccheo Damiano , Amenta Francesco
Published: January 2008

1 The influence of pre‐eclampsia on the density and pattern of dopamine D1‐like receptors was studied in frozen samples of the placental end of the umbilical artery by using radioligand binding and autoradiographic techniques in combination.

2 Analysis was performed on normotensive (n= 10) and pre‐eclamptic subjects (n= 9) undergoing caesarean delivery, using [3H]‐SCH 23390 as a ligand. Pre‐eclamptic patients received a low salt diet and were treated with magnesium sulphate and hydralazine. The possibility that this treatment may cause changes in the density of dopamine D1‐like receptors was evaluated by treating male Wistar rats in the same way and by determining [3H]‐SCH 23390 binding in sections of the kidney which represents an organ containing dopamine D1‐like receptors.

3 The density of dopamine D1‐like receptors of the umbilical artery, which are probably vasodilatory, was decreased in pre‐eclamptic compared with normotensive subjects. In contrast, the affinity of the radioligand for dopamine D1‐like receptors was not statistically different between normotensive and pre‐eclamptic subjects. Low salt diet, magnesium sulphate and hydralazine treatment did not affect [3H]‐SCH 23390 binding to sections of rat kidney. This suggests that changes in the density of dopamine D1‐like receptors in pre‐eclamptic patients are a specific phenomenon not dependent upon antihypertensive measures.

4 Analysis of the pharmacological profile of [3H]‐SCH 23390 binding to sections of the umbilical artery both in normotensive and pre‐eclamptic subjects indicates the labelling of dopamine D5 receptors.

5 These findings collectively suggest that the dopaminergic vasodilatory tone in the umbilical artery is impaired in pre‐eclampsia. The possible significance of these data should be clarified in future studies.
Skimmianine and related furoquinolines function as antagonists of 5‐hydroxytryptamine receptors in animals
Authors: Cheng Juei‐Tang , Chang Tzen Kwan , Chent Ih‐Sheng
Published: January 2008

1 Skimmianine, kokusaginine and confusameline, three furoquinolines extracted from the leaves of Evodia merrillii(Rutaceae), were investigated to characterize their selective effects on subtypes of 5‐hydroxytryptamine (5‐HT) receptors.

2 In the isolated membranes of rat cerebrocortex, using [3H]‐5‐HT and [3H]‐ketanserin as radioligands, skimmianine and the two other furoquinolines displaced radioligand bindings in a concentration‐dependent manner. Lower concentrations were required to affect [3H]‐ketanserin binding than [3H]‐5‐HT binding in the order skimmianine > kokusaginine > confusameline.

3 Furoquinolines inhibited 5‐HT‐induced contraction mediated by 5‐HT2 receptors in the presence of methiothepin in rat isolated aorta. Also, the combination of furoquinolines with ketanserin showed an additive antagonism.

4 These furoquinolines were inactive on the 5‐carboxamidotryptamine‐induced relaxation of guinea‐pig ileum, a 5‐HT1‐mediated event. However, 5‐HT‐induced contraction via 5‐HT2 receptors was reduced by these furoquinolines in a way similar to that in blood vessels.

5 The failure of these compounds to affect the 5‐HT‐induced Bezold–Jarisch‐like reflex in anaesthetized rats, the major .5‐HT3‐mediated action, ruled out an action on 5‐HT3 receptors.

6 The results obtained suggest that three furoquinoline alkaloids may act on 5‐HT receptors in animals, more selectively to the 5‐HT2 subtype, in the order of skimmianine > kokusaginine > confusameline.
Functional β‐adrenoceptors in the left atrium of normotensive and hypertensive rats
Authors: Doggrell Sheila A. , Surman Ailsa J.
Published: January 2008

1 The aim of the study was to characterize the functional β1‐ and β2‐adrenoceptors of the rat left atrium and to investigate how these functional β‐adrenoceptor responses were altered in hypertension. The contractile responses of the left atrium from Wistar‐Kyoto (WKY) and spontaneously hypertensive (SH) rats to isoprenaline, T‐0509 and procaterol were characterized. Subsequently, the effects of selective β1‐(bisoprolol) and β2 (ICI 118,551)‐adrenoceptor antagonists were investigated on these responses.

2 The maximal combined contractile responses of the rat left atrium to cardiac stimulation and CaCl2, isoprenaline, T‐0509 or procaterol were not altered by hypertension.

3 The sensitivities to CaCl2 (pD2 on WKY left atrium = 2.99), isoprenaline (8.82) and T‐0509 (8.84) were not altered by hypertension. There was an increase in sensitivity to procaterol from a pD2 value of 7.21 to 7.61 in the left atrium of the SH rat.

4 The basal tension induced by cardiac stimulation alone was inhibited by bisoprolol at ≤ 10−8M and by ICI 118,551 at ≤ 10−7M and this inhibitory effect is probably due to membrane stabilizing activity.

5 The pKB values for bisoprolol against isoprenaline, T‐0509 and procaterol on the WKY were 8.43, 8.68 and 8.18, respectively, and were not different from SH rat left atrium.

6 The pKB value for ICI 118,551 against isoprenaline was increased from 7.06 on the WKY to 7.44 on the SH rat left atrium. The pKB values for ICI 118,551 against T‐0509 and procaterol on the WKY were 7.18 and 8.14, respectively and were not significantly different from the SH rat left atrium values.

7 These results suggest that: (a) procaterol stimulates the β1‐, in addition to, the β2‐adrenoceptors of the rat left atrium; (b) functional β‐adrenoceptors are not altered in hypertension, and (c) there is probably an increase in the affinity of procaterol and isoprenaline for the β‐adrenoceptors which underlies the small increase in the functional β2‐adrenoceptor response in hypertension.
Asthma und Tuberkulose bei Kindern.
Authors: WALLGREN ARVID
Published: January 2008

Es ist nicht nachgewiesen, dass die Tuberkuloseinfektion eine erhohte Neipng zu Asthma mit sich bringt. Die Tuberkulosefrequenz bei asthmakranken Kindern ist bedeutend iiberschatzt worden. Asthma und Bronchialdriisentuberkulose kommen‐recht selten kouibiniert vor, jedoch ist ein Koiqdizierennicht etwas so Ungewohnliches, dass Anlass wilre, einen Antagonismus zwischen den beiden Krankheiten anzunehmen. In den Fallen, wo Asthma mit einer klinischen Hilustuberkulose kombiniert ist, hat man bisher wenig positive Griinde dafiir gehabt, die Entstehung der einen Krankheit mit der andern in Zusammenhang zu bringen. Asthmaanfdle von dem Typus, wie er bei gewohnlichem Bronchialasthma vorliegt, konnen jedoch in aeltenen Auanahmsfallen, wie drei vom Verf. beobachtete Fiille beweisen, durch eine Bronchialdriisentuberkulose hervorgerufen werden.
Necrosis adiposa neonatorum.
Authors: HARPøTH. Von HARALD
Published: January 2008

Es wird ein Fall von Fettgewebsnekrose bei einem Kind mitgeteilt; man bespricht die Diagnose und erwähnt die beiden anderen Leiden der Skleremkrankheit.

Es wird eine hypothetische Betrachtung über die Ätiologie angestellt.

Die Mikroskopie entspricht im wesentlichen der von Gelbjerg‐Hansen hier zu Lande zuerst beschriebenen und zeichnet sich durch verwischte Fettzellengrenzen, ← Ausfüllung← der Fettzellen, sowie durch eine reaktive Entzündung mit Riesenzellen aus.

Unser Fall scheint der zweite beschriebene Fall mit oberflächlicher Nekrose zu sein.
Scarlet fever and Diphtheria in Tonsillectomized Children.
Authors: NORDWALL ULF
Published: January 2008

In the Stockholm Hospital for Infectious Diseases the scarlet fever and diphtheria cases over a six year period have been studied with reference to the course of these diseases in tonsillectomized patients. 104 cases of scarlet fever and 71 cases of diphtheria all of whom had had previous tonsillectomies were compared with a suitable series of controls consisting of 3 times as many patients. The results in regard to the scarlet fever cases are as follows:

1. There probably exists no difference in regard to the severity of onset as estimated by the angina and eruption in tonsillectomized and non‐tonsillectomized individuals.

2. The number of cases with complications as well as the different complications occur on the whole in the same frequency in the two groups (No statistically determinable difference).

3. Tonsillectomized patients cause just as many infections as do the non‐tonsillectomized after they return to their homes, thus indicating that the contagiousness at the later stage of the disease is not dependent on the presence or absence of the tonsils.

4. Hemolytic streptococci can be demonstrated later in the convalescent period in non‐tonsillectomized than in tonsillectomized individuals.

The results in regard to the diphtheria cases are as follows:

1. Diphtheria of the pharynx is much more frequent among diphtheria patients with tonsils than among those who have had a tonsillectomy. Nasal diphtheria is common among the latter.

2. Malignant diphtheria occurs considerably oftener among non‐tonsillectomized than among tonsillectomized patients.

3. The frequency of complications is less among tonsillectomized than among non‐tonsillectomized patients.
Behandlung der Zuckerkrankheit im Kindesalter ohne Diäteinschränkungen.
Authors: SöDERLING. BERTIL
Published: January 2008

Wir haben 21 Diabetespatienten (Insulinfälle) im Alter von 3–34 Jahren ohne irgendwelche Diätrestriktionen be‐handelt; dabei sind wir von der Möglichkeit ausgegangen, dass der Mangel in der Inkretion in befriedigender Weise durch das artifizielle Insulin gedeckt wird. Die Dauer der Beob‐achtungszeit variiert gegenwärtig zwischen ½–2½ Jahren.

Bei der Behandlung wurde so gut wie ausschliesslich das subjektive und – so weit als möglich – auch das objektive

Wohlbefinden des Patienten berücksichtigt (Fragen: Durst, Müdigkeit, Fähigkeit zu Arbeitsleistungen, Appetit, Gewicht, Insulinbeschwerdei, Polyurie etc.), wofür ein azetonfreier Harn und eine Verineidung von hypogtykämischen Zuständen die grösste Rolle spielt.

Die Höhe des Blutzuckers und Menge des Harnzuckers sind sonst wenig berücksichtigt worden.

Die Behandltmg hatte den grössten Erfolg, und sie scheint sämtlichen Patienten ein leistungsfähiges Leben gegeben zu haben bei augenfälligem Wohlbefinden sowie bei einem so grossen Sicherheitsmarginal gegen Infektionen, Azidose und Insulin‐beschwerden, dass in 16 Fällen nach der Umstellung überhaupt kein Spitalsaufenthalt vorkam, und dass in keinem Falle Präkoma oder Koma auftrat. Auch die Insulinbeschwerden waren viel seltener als bisher und kamen nur in einigen wenigen Fällen vor.

Die Behandlung diirfte daher besonders zweckmässig sein, wenn der Pat. in einer unintelligenten und unzuverlässigen Umgebung lebt, und wenn die Kontrolle der Patienten wegen weiter Entfernung ihres Wohnortes oder aus anderen Gründen Schwierigkeiten bereitet.

Über die Insulinfragen, den KH‐Verbrauch, die Blut‐zucker‐ und Harnzuckerverhältnisse, die körperliche Entwick‐lung und unsere allgemeinen Eindrücke der Freikostbehandlung ist in besonderen Kapiteln berichtet, denen ein geschichtlicher Überblick vorausgeht.

Ein Schaden am Insulinapparat infolge eventueller Beanspruchungen durch die Kost konnte nicht festgestellt werden. Zwei Fälle (6 und 13) zeigten nach einem Jahre einen augenfällig gesteigerten Insulinbedarf, während dieser bei den übrigen Fällen eher erstaunlich konstant war, dies, wenn man von den Fällen 1, 5 und 15 absieht, bei welch en der gesteigerte Insulinbedarf anderen Ursachen zuzuschreiben ist.

Unter 17 Fällen älteren Datums wurde für 9 bei der Umstellung auf freie Kost die frühere Insulinmenge beibe‐halten, in 4 Fällen wurde sie gesteigert und in 4 Fällen her‐abgesetzt. Von sämtlichen Fällen erhielten 7 täglich 3 Insu‐lindosen, 12 täglich 2 Dosen, und die übrigen 2 tgl. 1 Dosis.

Die körperliche und sexuelle Entwicklung ist sichtlich in normaler Weise fortgeschritten.

Schliesslich ist über 7 Fälle berichtet, bei welchen Kohlen‐hydratverbrauch, Haru‐ und Blutzucker eingekender verfolgt wurden.