bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE MODE OF ACTION AT THE MOUSE NEUROMUSCULAR JUNCTION OF THE PHOSPHOLIPASE A‐CROTAPOTIN COMPLEX ISOLATED FROM VENOM OF THE SOUTH AMERICAN RATTLESNAKE
Authors: HAWGOOD BARBARA J. , SMITH J.W. 
Published: July 2012

Phospholipase A2‐crotapotin complex (P‐C complex) isolated from the venom of Crotalus durissus terrificus induced an irreversible blockade of neuromuscular transmission when twitch tension was measured in the mouse phrenic nerve‐hemidiaphragm preparation in vitro at 37°C.
A similar concentration of the phospholipase A2 (10 μg/ml) alone did not affect neuromuscular transmission and no priming action was detected on later addition of crotapotin.
The rate of neuromuscular blockade induced by P‐C complex (15 μg/ml) was not altered by raising the frequency of nerve stimulation. Lower temperatures markedly increased the time of onset and reduced the rate of blockade (Q10 (27‐37°C) of 4.4) whilst replacement of Ca by Sr in the medium prevented this activity. These latter results suggest that enzymatic activity is important in the neurotoxicity of the complex.
A myotoxic action was shown by 30 μg/ml P‐C complex and 30 μg/ml phospholipase A2.
P‐C complex (150 μg) was injected into the tail vein of mice and the intoxicated hemidiaphragm preparation removed for intracellular recording at 25°C.
In fully intoxicated hemidiaphragms, resting membrane potentials were unaltered and endplate potentials (e.p.ps) varied in average amplitude from zero to less than 3 mV.
Miniature endplate potential (m.e.p.p.) frequency was lower at fully poisoned endplates than at controls; the frequency rose during a 50 Hz tetanus but was unaffected by either raising external K or the application of the Ca‐ionophore A23187.
E.p.ps were recorded in partially intoxicated hemidiaphragms with (+)‐tubocurarine (0.5‐1.0 μg/ml) added to prevent contraction. Evoked release was abnormal as 50 Hz tetanus elicited e.p.ps of very variable amplitude, no facilitation of response was shown to paired stimuli, and tetraethylammonium (0.5 mM) failed to increase e.p.p. amplitudes.
M.e.p.ps and e.p.ps were recorded at partially poisoned endplates in low Ca‐high Mg solution. A reduction in the quantal content of evoked transmitter release was observed in comparison with controls.
M.e.p.ps recorded at partially and at fully intoxicated endplates showed an altered amplitude distribution with a higher proportion of large potentials.
It is concluded that P‐C complex has a presynaptic site of action and may interfere with depolarization ‐ secretion coupling at the motor nerve terminals.
PATHWAYS OF PROSTAGLANDIN F2α METABOLISM IN MAMMALIAN KIDNEYS
Authors: HOULT J.R.S. , MOORE P.K. 
Published: July 2012

High‐speed cytoplasmic supernatants of rat, rabbit, pig and guinea‐pig kidneys were prepared and the metabolism of 10 μg/ml prostaglandin F2α labelled with [3H1‐9β]‐prostaglandin F2α studied by thin layer radiochromatography and bioassay.
The metabolism of prostaglandin F2α measured by radiochromatography parallels biological inactivation in all species except the rabbit.
Kidneys metabolize prostaglandin F2α by two divergent pathways, yielding a mixture of prostaglandin E and F metabolites.
15‐Hydroxyprostaglandin dehydrogenase and prostaglandin Δ‐13 reductase are present in all species in characteristic proportions. Thus prostaglandin F2α is metabolized sequentially to 15‐keto prostaglandin F2α and 13,14‐dihydro‐15‐keto prostaglandin F2α. The rate and profile of formation of these metabolites is species‐dependent.
13,14‐Dihydro‐15‐keto prostaglandin F2α is the principal prostaglandin F series metabolite in all species.
Pig and guinea‐pig kidney contain an unidentified enzyme which converts 13,14‐dihydro‐15‐keto prostaglandin F2α to 13,14‐dihydro prostaglandin F2α.
Rat kidney contains a high concentration of a prostaglandin 9‐hydroxy dehydrogenase which converts 13,14‐dihydro‐15‐keto prostaglandin F2α to 13,14‐dihydro‐15‐keto prostaglandin E2.
Rabbit kidney contains a novel 9‐hydroxydehydrogenase which oxidises prostaglandin F2α directly to E2, thus producing a compound with more potent renal actions. The possible implications of this enzyme for kidney homeostasis are discussed.
THE DISTRIBUTION OF METHIONINE‐ENKEPHALIN AND LEUCINE‐ENKEPHALIN IN THE BRAIN AND PERIPHERAL TISSUES
Authors: HUGHES J. , KOSTERLITZ H.W. , SMITH T.W. 
Published: July 2012

A method is described for the rapid extraction of opioid peptides from the brain and other tissues. The method is based on acid extraction of tissues followed by adsorption of the extract onto Amberlite XAD‐2 resin. Elution with methanol separates the enkephalins and α‐endorphin from β‐endorphin.
Over 90% of the opioid peptide activity isolated from brain and gut of several species by our method was due to methionine‐ and leucine‐enkephalin. In contrast, the major opioid peptide activity recovered from the pituitary was due to peptides of much greater mol. wt. than the enkephalins.
An opioid peptide with properties unlike those of the known endorphins or enkephalins was present in brain extracts. This peptide, termed ∍‐endorphin, has an apparent mol. wt. of 700 to 1200; it constituted between 5 to 10% of the total opioid activity in our extracts.
A differential assay of methionine‐ and leucine‐enkephalin was made either by destroying methionine‐enkephalin activity with cyanogen bromide or by separating the peptides by thin layer chromatography.
The ratio of methionine‐enkephalin to leucine‐enkephalin varied greatly in different brain regions. The highest proportions of leucine‐enkephalin were found in the cerebral cortex and hippocampus.
Formaldehyde perfusion and fixation of the brain in vivo had no significant effect on the brain content of enkephalin, indicating that proteolytic breakdown is not a major problem in the extraction of these peptides.
It is suggested that the enkephalins may have a neurotransmitter role in both brain and peripheral tissues and that methionine‐ and leucine‐enkephalin may subserve separate neuronal functions.
THE SPECIFICITY OF OESTROGEN RECEPTOR IN BRAIN, PITUITARY AND UTERUS
Authors: GINSBURG M. , MACLUSKY N.J. , MORRIS I.D. , THOMAS P.J. 
Published: July 2012

The specificity of oestrogen receptor in rat brain regions (hypothalamus, amygdala and cortex), pituitary and uterus was studied by measurement of the inhibition of 17β‐oestradiol high affinity binding in cytosol, in the presence of unlabelled putative inhibitors of binding.
Binding was inhibited only by those of the compounds tested that possessed oestrogen agonist or antagonist activity. The affinities were estimated and the ranking order of the compounds was the same in all tissue sources of cytosol and corresponded to the ranking order of agonist or antagonist potency.
There were some significant differences between some of the estimated affinities in different tissues, these being seen most commonly between pituitary and hypothalamus on one hand and uterus on the other.
The possibility of heterogeneity of oestrogen receptor is discussed.
THE EFFECT OF UPTAKE BY ADRENERGIC NERVE TERMINALS ON THE SENSITIVITY OF ARTERIAL VESSELS TO TOPICALLY APPLIED NORADRENALINE
Authors: MARSHALL JANICE M. 
Published: July 2012

Direct observations were made of the rat mesenteric vasculature in vivo. They showed a gradual increase in the sensitivity to topically applied noradrenaline from the larger arteries to the precapillary arterioles which was paralleled by a gradual decrease in the density of the adrenergic innervation.
Both cocaine and chronic denervation increased the sensitivity to noradrenaline of the innervated arterial vessels, approximately in proportion to the density to their innervation. They did not affect the sensitivity of the non‐innervated precapillary arterioles.
It is concluded that the sensitivity gradient to topically applied noradrenaline results mainly from the uptake of the applied catecholamine by the perivascular nerve terminals.
ASSESSMENT OF THE SELECTIVITY OF OPC‐2009, A NEW β2‐ADRENOCEPTOR STIMULANT, BY THE USE OF THE BLOOD‐PERFUSED TRACHEA in situ AND OF THE ISOLATED BLOOD‐PERFUSED PAPILLARY MUSCLE OF THE DOG
Authors: HIMORI N. , TAIRA N. 
Published: July 2012

The potency and selectivity of 5‐(1‐hydroxy‐2‐isopropylamino)butyl‐8‐hydroxy carbostyril hydrochloride hemihydrate (OPC‐2009), a new β2‐adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood‐perfused tracheal preparations in situand of blood‐perfused papillary muscle preparations of the dog. All drugs were injected intra‐arterially.
All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose‐dependent manner. The four drugs produced a dose‐dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC‐2009 and trimetoquinol was long. These effects were antagonized by propranolol.
Dose‐response curves to the four drugs for tracheal relaxation were almost parallel. OPC‐2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation.
Dose‐response curves to the four drugs for tracheal vasodilatation were also parallel. OPC‐2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline.
Slopes of the dose‐response curves to the four drugs for increased developed tension were not parallel; that of OPC‐2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC‐2009 were about 18, 570 and 2400 times less potent than isoprenaline.
Selectivity calculated from relative potencies indicate that OPC‐2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle.
The high potency and selectivity of OPC‐2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma.
The present results are also compatible with the concept that β1‐adrenoceptors in cardiac muscle and β2‐adrenoceptors in tracheal and vascular smooth muscle can be distinguished. Furthermore, the results revealed that the β‐adrenoceptors mediating tracheal relaxation and vasodilatation may also be different.
THE INFLUENCE OF PROSTAGLANDINS ON NORADRENALINE‐INDUCED VASOCONSTRICTION IN ISOLATED PERFUSED MESENTERIC BLOOD VESSELS OF THE RAT
Authors: COUPAR I.M. , MCLENNAN P.L. 
Published: July 2012

The report of the depression by indomethacin of vasoconstrictor responses to noradrenaline and their partial restoration by prostaglandin E2 (PGE2) and PGE1 in rat isolated perfused mesenteric blood vessels was investigated. The further suggestion that prostaglandins may be necessary for the combination of noradrenaline with the α‐adrenoceptor in this tissue was also studied.
The reported depression by indomethacin was confirmed and was further shown to be in the form of a concentration‐dependent flattening of the noradrenaline concentration‐effect curve.
A concentration‐dependent restorative effect was observed for all prostaglandins studied. The decreasing order of potency for the restoration towards normal of the indomethacin‐depressed responses to noradrenaline was: PGE2, PGE1, PGA1, PGF2α, PGA2.
The prostaglandins studied were not uniform in their restorative actions and could be separated into two groups. PGE2 and PGE1 restored responses towards the control level whereas PGA1, PGA2 and PGF2α increased responses to an above control level and did so over a smaller concentration range. The possibility of several prostaglandin receptors is discussed.
At concentrations equi‐effective in restoring depressed responses to control levels PGA1 but not PGE2, caused a parallel shift of the noradrenaline concentration‐effect curve to the left and a small, gradual rise in the basal perfusion pressure.
The reason for the differing effects remains obscure but does not seem to involve a change in the α‐adrenoceptor as indicated by the pA2 of phentolamine. Furthermore, the restorative and potentiating effect of PGA1 is not mediated by blockade of neuronal uptake of noradrenaline.
It appears that prostaglandins are required for the vasoconstrictor action of noradrenaline in rat mesenteric blood vessels and that this effect is distal to the drug‐receptor interaction. The possible involvement of prostaglandins with intracellular calcium ions is discussed.
α‐ADRENOCEPTORS IN THE MOUSE VAS DEFERENS AND THEIR EFFECTS ON ITS RESPONSE TO ELECTRICAL STIMULATION
Authors: MARSHALL I. , NASMYTH P.A. , NICHOLL CLAIRE G. , SHEPPERSON N.B. 
Published: July 2012

Noradrenaline (ID50, 0.75 μM) and clonidine (ID50, 2.8 nM) produced a dose‐related inhibition of the twitch response of the isolated vas deferens of the mouse to electrical stimulation, their effectiveness decreasing as frequency of stimulation increased from 0.2 to 16 hertz.
Phenylephrine (1.0‐3.0 μM) produced a dose‐related contraction of the mouse isolated vas deferens and potentiated the responses to field stimulation.
Yohimbine (10 nM) antagonized the inhibitory effects of noradrenaline and clonidine, but had no effect on the motor activity of phenylephrine. At a concentration of 128 nM yohimbine potentiated the twitch response by 110% at 1 Hz, but its effectiveness decreased with increasing frequency of stimulation up to 16 hertz.
Thymoxamine (0.3 μM) antagonized the effects of phenylephrine, but not those of clonidine.
From a consideration of the known characteristics of pre‐ and postsynaptic α‐adrenoceptors, it is concluded that the inhibitory effect of noradrenaline is produced by stimulation of the former and the effects of phenylephrine by stimulation of the latter.
EVIDENCE FOR THE PARTICIPATION OF β1‐ADRENOCEPTORS IN ISOPRENALINE‐INDUCED RENIN RELEASE FROM RAT KIDNEY SLICES in vitro
Authors: DESAULLES E. , MIESCH F. , SCHWARTZ J. 
Published: July 2012

The inhibitory effects were studied of 4 β‐adrenoceptor antagonists against renin release induced by isoprenaline (0.5 m̈mol/1) in rat kidney slices. Additionally the pA2 values of these 4 drugs were measured against isoprenaline in guinea‐pig isolated atria and trachea (against β1‐ and β2‐adrenoceptors respectively).
When employed at a concentration of 2 nmol/1 propranolol and atenolol significantly inhibited renin release (P < 0.001 and P < 0.01) whereas practolol and IPS 339 [t‐butyl‐amino‐3 ol‐2 propyl) oximino‐9 fluorene] had little effect.
A positive correlation was shown between the degree of inhibition of renin release and the pA2 of the antagonists at the β1‐adrenoceptors.
When practolol and IPS 339 were used in equipotent molar concentrations to propranolol for the β1‐adrenoceptors they inhibited renin release.
The results suggest that the adrenoceptor involved in the renin release induced by isoprenaline in the rat kidney is of the β1‐type.
EFFECTS OF DRUGS ON THE ACCUMULATION AND SPONTANEOUS RELEASE OF NORADRENALINE IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: DOGGRELL S.A. , WOODRUFF G.N. 
Published: July 2012

The ability of drugs to inhibit noradrenaline accumulation and to release noradrenaline was studied in the isolated anococcygeus muscle of the rat.
Noradrenaline, tyramine, 2‐amino, 6,7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene (ADTN), 2‐amino, 6,7‐dimethoxy‐1,2,3,4‐tetrahydronaphthalene (dimethyl ADTN), and 5‐hydroxytryptamine were all potent inhibitors of noradrenaline accumulation and potent releasers of noradrenaline. ADTN was accumulated by the rat isolated anococcygeus muscle.
Amphetamine and desipramine were potent inhibitors of noradrenaline accumulation but poor releasers of noradrenaline.
Methoxamine, oxymetazoline, acetylcholine, and angiotensin were poor inhibitors of noradrenaline accumulation and did not release noradrenaline.
The mechanism of action of these drugs is discussed.
PROSTACYCLIN (PGI2) INHIBITS THE FORMATION OF PLATELET THROMBI IN ARTERIOLES AND VENULES OF THE HAMSTER CHEEK POUCH
Authors: HIGGS E.A. , HIGGS G.A. , MONCADA S. , VANE J.R. 
Published: July 2012

Isolated rings of hamster aorta produced an unstable substance which inhibited platelet aggregation in vitro and had the same characteristics as prostacyclin.
Prostacyclin inhibited adenosine diphosphate (ADP)‐induced aggregation of hamster platelets in vitro.
The effects of prostacyclin on ADP‐induced platelet thrombi in the microcirculation of the hamster cheek pouch were studied with a television microscope.
Prostacyclin caused a dose‐dependent increase in the time of iontophoretic application of ADP which was required to induce platelet thrombi formation and embolization in venules (30 to 40 um diameter).
Prostacyclin caused a dose‐dependent reduction in the total time during which ADP‐induced thrombi were observed following local electrical damage to arterioles (40 to 80 um diameter).
Thrombus formation in venules and arterioles was abolished by 500 ng/ml prostacyclin in the Krebs solution superfusing the hamster cheek pouch.
Prostacyclin was approximately twenty times more potent than prostaglandin Ei in preventing thrombus formation in the microcirculation.
EFFECTS OF NICOTINE ON CARDIAC PROSTAGLANDIN AND PLATELET THROMBOXANE SYNTHESIS
Authors: WENNMALM AKE 
Published: July 2012

Rabbit hearts were perfused with a solution containing [14C]‐arachidonic acid (AA) and various concentrations of nicotine (3 × 10−8 to 3 × 10−5m). The venous effluent was collected and extracted for lipid acid material, which was subsequently subjected to thin layer radiochromatography.
Human platelets were incubated with nicotine (10−8 to 10−4m), in the absence or presence of unlabelled AA. The amount of smooth muscle stimulating activity resulting from 30 s of incubation was tested on a rabbit aortic strip.
In hearts perfused with [14C]‐AA; nicotine induced a dose‐related depression of the release of [14C]‐6‐keto‐prostaglandin F1a, and a parallel increase in the release of [14C]‐prostaglandin E2.
Nicotine neither induced synthesis of thromboxane in human platelets, nor affected the platelet synthesis of thromboxane induced by AA.
It is suggested that nicotine affects the metabolism of prostaglandin endoperoxides in the heart by inhibiting their conversion to prostacyclin and facilitating, directly or indirectly, the formation of prostaglandin E2.
MODULATION OF SYMPATHETIC TRANSMISSION BY NEURONALLY‐RELEASED DOPAMINE
Authors: HOPE W. , MAJEWSKI H. , McCULLOCH M.W. , RAND M.J. , STORY D.F. 
Published: July 2012

When rabbits were pretreated with Fla‐63, there was a marked inhibition of dopamine‐β‐hydroxylase such that, after incubation of the ear arteries with [3H]‐dopamine, 47.2% of the tritium in the tissue was retained as unchanged dopamine.
[3H]‐dopamine was released by stimulation of the sympathetic nerves in ear arteries taken from rabbits pretreated with Fla‐63 and incubated with [3H]‐dopamine.
The dopamine antagonists metoclopramide (1.0 μm) and ergometrine (1.0 μm) enhanced the stimulation‐induced efflux of tritium in ear arteries taken from rabbits pretreated with Fla‐63 and incubated with [3H]‐dopamine, but not when the arteries were incubated with [3H]‐noradrenaline.
These results suggest that if dopamine is present in the transmitter stores, it can be released by stimulation of the sympathetic nerves, and if the amount is adequate, it can activate an inhibitory feedback loop where prejunctional dopamine receptors are present.
THEOPHYLLINE ANTAGONIZES SOME EFFECTS OF PURINES IN THE INTESTINE BUT NOT THOSE OF INTRAMURAL INHIBITORY NERVE STIMULATION
Authors: SMALL R.C. , WESTON A.H. 
Published: July 2012

Hyoscine‐ and guanethidine‐treated preparations of longitudinal muscle of rabbit duodenum, guinea‐pig taenia caeci and fundic strip relaxed when exposed to noradrenaline, adenosine, adenosine triphosphate (ATP) or to field stimulation of their intramural nerves.
In guinea‐pig taenia caeci and fundus, theophylline 100 μmol/l had no effect on responses to noradrenaline, adenosine, ATP and intramural nerve stimulation.
In rabbit duodenum, theophylline 100 μmol/l antagonized some responses to adenosine but had no effect on responses to noradrenaline, ATP and intramural nerve stimulation.
Theophylline 1 mmol/l itself relaxed the intestinal tissues and in the fundic strip and taenia caeci, these relaxant effects were associated with abolition of spike activity and cellular hyperpolarization. In the taenia caeci, the amplitude of inhibitory post‐junctional potentials was reduced.
Theophylline 1 mmol/l antagonized the twitch suppression produced by adenosine and ATP in the transmurally‐stimulated guinea‐pig ileum but not that evoked by noradrenaline.
It is concluded that theophylline can selectively antagonize some actions of purines in the intestine but that it does not specifically antagonize the effects of intramural inhibitory nerve stimulation.
HYDROXY ANALOGUES OF OXYTOCIN AND OF LYSINE‐VASOPRESSIN
Authors: BISSET G.W. , CHOWDREY H.S. , HOPE D.B. , NILWISES N. , WÄLTI M. 
Published: July 2012

Synthetic analogues of oxytocin and of lysine‐vasopressin with an hydroxyl group in either the l or d configuration replacing the primary amino group have been tested for biological activity.
[1‐l(‐2‐Hydroxy‐3‐mercaptopropanoic acid)] oxytocin ([l‐Hmp1]oxytocin) was 1.5 to 2 times more potent than oxytocin on the rat uterus in situ, the rat mammary strip and the rat mammary gland in situ and 3 times more potent on the rat isolated uterus.
The pressor activity of [1‐(l‐2‐hydroxy‐3‐mercaptopropanoic acid)‐8‐lysine]vasopressin ([l‐Hmp1, Lys8] vasopressin) was 2.2 and the antidiuretic activity 2.1 times that of lysine‐vasopressin.
The [d‐Hmp1] analogues of oxytocin and vasopressin were much less potent than the [l‐Hmp1] analogues.
The responses to oxytocin and its hydroxy analogues in vivo were qualitatively indistinguishable but the pressor and antidiuretic responses to the hydroxy analogues of lysine‐vasopressin were prolonged compared with those to the parent hormone.
The hydroxy analogues of oxytocin and lysine‐vasopressin were not inactivated by pregnancy plasma oxytocinase.
The results are discussed in relation to the importance of the primary amino group for the biological activity and metabolism of the neurohypophysial hormones.
THE EFFECTS OF DEPRIVATION OF PROSTAGLANDIN PRECURSORS ON VASCULAR SENSITIVITY TO ANGIOTENSIN II AND ON THE KIDNEY IN THE PREGNANT RABBIT
Authors: O'BRIEN P.M. SHAUGHN , PIPKIN FIONA BROUGHTON 
Published: July 2012

Pregnant rabbits were deprived of essential fatty acids from day ten of pregnancy, and results compared with a control group on a normal diet.
At term, cannulation of jugular and carotid vessels was performed under anaesthesia, to study the vascular sensitivity to angiotensin II and basal blood pressure.
Plasma renin levels, urinary electrolytes and protein were measured.
Placental and renal tissue was examined histologically.
Though no changes were found in tissues, blood or urine, a markedly significant increase in response to angiotensin II was found in the group deprived of essential fatty acids. This parallels the findings in vascular response in human pre‐eclampsia.