bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF PROSTAGLANDIN E2 AND A PROSTAGLANDIN ENDOPEROXIDE ANALOGUE ON NEUROEFFECTOR TRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE
Authors: TIMIMI KHAWLA S. AL , BEDWANI J.R. , STANTON A.W.B.
Published: July 2012

Investigations were made into the effects of prostaglandin E2 (PGE2) and a prostaglandin endo‐peroxide analogue (Upjohn compound U‐46619) on the responses of the rat anococcygeus muscle to field stimulation of the intrinsic sympathetic nerves, and to exogenous noradrenaline. The effects of PGE2 on responses to stimulation of intrinsic inhibitory nerves were also studied.

PGE2 (5.6 × 10−8 or 2.8 × 10−6mol/l) decreased motor (sympathetic) responses to field stimulation at all frequencies tested (2 to 24 Hz). The prostaglandin also reduced the inhibitory responses to field stimulation, seen when the tone of the preparation had been raised and its sympathetic innervation had been blocked by guanethidine. However, these inhibitory responses were also reduced by other spasmogens (carbachol and 5‐hydroxytryptamine) which, like PGE2, further increased the tone of guanethidine‐treated preparations.

At a concentration of 5.6 × 10−8 mol/1, PGE2 had no effect on responses to noradrenaline, whereas at a fifty‐fold higher concentration the prostaglandin potentiated these.

Unlike PGE2, U‐46619 (5.6 × 10−8 mol/1) greatly potentiated motor responses to field stimulation, at frequencies from 0.75 to 24 Hz. This effect did not represent a specific facilitation of sympathetic neurotransmission, as responses to carbachol and 5‐hydroxytryptamine, as well as to noradrenaline, were also potentiated.

The results are discussed in relation to the effects of prostaglandins and prostaglandin endoperox‐ides on neuroeffector transmission in other sympathetically innervated tissues. It is concluded that PGE2 inhibits sympathetic neurotransmission in the rat anococcygeus muscle by a prejunctional action, whereas the predominant effect of U‐46619 is direct excitation of the muscle. The effect of PGE2 on inhibitory responses to field stimulation may represent an interference with inhibitory neuroeffector transmission in this tissue, or may simply be a consequence of the spasmogenic action of the prostaglandin.
THE UPTAKE AND RELEASE OF [3H]‐2‐AMINO‐6,7‐DIHYDROXY1,2,3,4‐TETRAHYDRONAPHTHALENE (ADTN) BY STRIATAL NERVE TERMINALS
Authors: DAVIS A. , ROBERTS P.J. , WOODRUFF G.N.
Published: July 2012

A study has been made of the uptake and release of [G‐3H]‐2‐amino 6,7‐dihydroxy‐1, 2,3,4‐tetra‐hydronaphthalene (ADTN) by crude striatal synaptosomes of the rat.

Uptake was rapid, temperature‐dependent and could be suppressed by a variety of metabolic inhibitors.

The Michaelis‐Menten kinetics indicated the presence of two distinct transport systems in the striatum which were of much higher capacity than those found in the cerebellum, which lacks dopaminergic innervation.

Uptake of [3H]‐ADTN was strongly inhibited by dopamine and the two potent dopamine‐uptake inhibitors, benztropine and nomifensine, but only weakly by imipramine and amphetamine (the latter in non‐reserpine‐treated animals).

Accumulated [3H]‐ADTN could be released from striatal slices by elevated K+. A similar release was evoked upon the addition of the ionophore, A23187.

The most potent releaser of [3H]‐ADTN was (+)‐amphetamine. This effect occurred at concentrations inactive against ADTN uptake. The neuroleptic ris‐flupenthixol produced an inhibition of the spontaneous release.

It is concluded that [3H]‐ADTN is accumulated preferentially into areas of the rat brain rich in dopamine. The pharmacological specificity of the uptake suggests that it is a good substrate for the dopamine carrier. Following uptake, [3H]‐ADTN may be released by K+ and a calcium ionophore, which raises the possibility that ADTN might act as a false transmitter.
THE EFFECT OF BACLOFEN ON α‐FLUPENTHIXOL‐INDUCED CATALEPSY IN THE RAT
Authors: DAVIES J.A. , WILLIAMS J.
Published: July 2012

α‐Flupenthixol (α‐FPT; 0.2 mg/kg i.p.) when administered to rats produced catalepsy.

Baclofen (10 mg/kg i.p.) given 30 min after α‐FPT had a biphasic effect on the catalepsy. Initially there was a potentiation of the effect, followed by a significant attenuation of the degree of catalepsy.

Possible mechanisms of action are discussed.
ANTI‐DEPRESSANT ACTION OF CAESIUM CHLORIDE AND ITS MODIFICATION OF CHLORPROMAZINE TOXICITY IN MICE
Authors: MESSIHA F.S.
Published: July 2012

Adult male mice were treated with caesium chloride (1.0 mEq/kg, i.p.) once daily for 54 consecutive days before administration of a single dose of reserpine (2.0 mg/kg) or (+)‐amphetamine (1.0 mg/kg). Pretreatment with caesium chloride resulted in potentiation of amphetamine‐produced enhancement of motility and in antagonism of reserpine‐induced behavioural depression in mice as measured by a locomotor activity test, compared to the respective controls.

Chronic administration of caesium chloride (1.0 mEq/kg daily) with gradual dose build‐up of chlorpromazine (up to 50 mg kg−1 day−1) counteracted chlorpromazine‐produced mortality in mice.

The results suggest an antidepressant property for Cs+ and the combined treatment of caesium chloride with chlorpromazine might have a clinical application, i.e. in the management of chlorpromazine‐induced adverse reactions.
RAT ISOLATED PHRENIC NERVE‐DIAPHRAGM PREPARATION FOR PHARMACOLOGICAL STUDY OF MUSCLE SPINDLE AFFERENT ACTIVITY: EFFECT OF OXOTREMORINE
Authors: GANGULY D.K. , NATH D.N. , ROSS H‐G. , VEDASIROMONI J.R.
Published: July 2012

Muscle spindle afferent discharges exhibiting an approximately linear length‐frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve‐diaphragm preparation of the rat.

Muscle spindle afferent discharges could be identified by their characteristic ‘spindle pause’ during muscle contraction and by their response to succinylcholine.

Cholinergic influence on spontaneous and stretch‐induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)‐Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles.

Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium‐3 and (+)‐tubocurarine failed to affect the rate of spontaneous and stretch‐induced spindle discharges.

Oxotremorine markedly increased the rate of spontaneous and stretch‐induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium‐3 and (+)‐tubocurarine.

These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents are hyperactive in Parkinsonian patients.
A COMPARISON OF DRUG‐INDUCED RESPONSES ON RAT TRACHEAL BRONCHIAL AND LUNG STRIP in vitro PREPARATIONS
Authors: BURNS J.W. , DOE J.E.
Published: July 2012

A preparation of rat trachea and a new preparation of rat bronchi are described. Both preparations are fluid‐filled and the intraluminal pressure is monitored.

A preparation of rat peripheral airways, the lung strip, is described. The preparation consists of a thin strip of lung parenchyma which is supervised, and contractions monitored isotonically.

The rat trachea and bronchi have no intrinsic tone but increases in pressure are elicited in response to methacholine. The preparations relax in response to isoprenaline and aminophylline in the presence of a methacholine‐induced contraction. Both preparations respond weakly and show tachyphylaxis to 5‐hydroxytryptamine (5‐HT).

The lung strip contracts with equal magnitude to methacholine and 5‐HT. It exhibits intrinsic tone which is inhibited by indomethacin and relaxed by isoprenaline.
ENHANCEMENT OF A NOCICEPTIVE REACTION BY OPIOID ANTAGONISTS IN MICE
Authors: JACOB J.J.C. , RAMABADRAN K.
Published: July 2012

The opioid antagonists, naloxone, GPA 2163, levallorphan and Mr‐2266 reduced the latency of the jumping reaction of mice in the hot plate test. The (+)‐isomers of levallorphan and Mr‐2266 which are devoid of antagonistic activity did not increase this latency.

In the same nociceptive reaction test, the enhancing effect of naloxone progressed in a dose‐range similar to that required for the antagonism by naloxone of the depressive action of morphine.

The facilitatory effect of naloxone was not blocked by the previous administration of morphine or etorphine but it was prevented by pretreatment with a high dose of buprenorphine.

The antagonism by naloxone of morphine and of buprenorphine did not follow the same pattern.

The factors which are or may be involved in the efficacy of naloxone in enhancing nociceptive reactions are discussed.

The enhancing effect of naloxone may be due to an antagonism of endogenous ligands for the opiate receptor. If so, these ligands would be involved in reaction to but not in perception of nociceptive stimuli which need not be harmful ones.
SELECTIVE EFFECTS OF MORPHINE ON THE NOCICEPTIVE RESPONSES OF THALAMIC NEURONES IN THE RAT
Authors: HILL R.G. , PEPPER CHRISTINE M.
Published: July 2012

The effects of intravenous morphine on the firing of single sensory neurones in the thalamus of the anaesthetized rat are described.

Low doses (0.38 to 2.00 mg/kg) of morphine depressed the excitation of nucleus lateralis neurones produced by natural noxious stimuli but were without effect on spontaneous activity. The excitation of some of these neurones by iontophoretically applied acetylcholine or glutamate was also depressed by morphine. These effects were reversed by intravenous (0.25 to 1.17 mg/kg) but not iontophoretically applied (50 to 200 nA) naloxone.

Similar or higher doses of morphine (0.58 to 5.07 mg/kg) did not prevent the excitation of ventrobasal thalamic neurones by non‐noxious stimuli.

The possibility of a direct action of intravenous morphine in the thalamus is discussed.
POTENTIATION OF NERVE‐INDUCED BLADDER RESPONSES BY TETRAETHYLAMMONIUM IN RELATION TO JUNCTIONAL AND EXTRAJUNCTIONAL MUSCARINIC RECEPTORS
Authors: CARPENTER F.G.
Published: July 2012

The single stimulus responses elicited in the rat urinary bladder were enhanced up to 3 fold by tetraethylammonium chloride (TEA) in the range 2.5 to 10 mm. Responses elicited by repetitive stimulation at 20 Hz were potentiated much less by 2.5 and 5 mm TEA; 10 mm TEA depressed the responses to less than control levels.

The responses elicited in preparations treated with tetrodotoxin or botulinum toxin during the 20 Hz stimulus trains were one third to one half of control, while single stimulus responses were abolished altogether. After 10 mm TEA the response to the 20 Hz stimulus trains were near control but the single stimulus responses were not restored at all.

The single stimulus response of control and of TEA‐treated bladder preparations were unaffected by atropine (2 × 10−6m) but responses elicited by a 20 Hz stimulus train were reduced more than 40% by atropine. After 5 mm TEA the responses to the 20 Hz stimulus trains that had been partially blocked by atropine were immediately restored to near control levels.

The responses of bladders to carbachol were dose‐dependent in the range 10−6 to 10−5m and were atropine‐sensitive. After 5 mm TEA the means of the responses produced by graded doses of carbachol were less than control; muscarinic receptors that were blocked by TEA are probably also atropine‐sensitive.

It is suggested that muscarinic receptors in the rat urinary bladder may be divided into: (1) junctional receptors that are resistant to atropine and may be indirectly affected by TEA and (2) extrajunctional receptors that are blocked by atropine and may be directly affected by TEA.
ALTERATION OF MEDULLARY RESPIRATORY UNIT DISCHARGE BY IONTOPHORETIC APPLICATION OF PUTATIVE NEUROTRANSMITTERS
Authors: KIRSTEN EDWARD B. , SATAYAVIVAD J. , ST. JOHN WALTER M. , WANG S.C.
Published: July 2012

Cats with midcollicular decerebration were vagotomized, paralyzed and artificially ventilated. Phrenic nerve activity was recorded as an index of central respiratory rhythm. Medullary respiratory neurones and non‐respiratory cells located in approximation to the ventral respiratory nucleus were tested for their responsiveness to iontophoretically applied γ‐aminobutyric acid (GABA), acetylcholine (ACh) and glutamate.

GABA tended to inhibit, whereas ACh and glutamate excited activity both of respiratory and non‐respiratory units. Some phase‐spanning respiratory unit activities were converted to phasic discharge patterns linked to either inspiration or expiration concomitant with application of low GABA doses. Appropriate applications of GABA also resulted in a complete cessation of the respiratory or non‐respiratory neuronal activities.

While application of ACh or glutamate induced continuous firing in phasic, phase‐spanning respiratory neurones, the periodic discharge patterns of inspiratory or expiratory units was not altered by ACh or, in many instances, by glutamate. Only at high doses of glutamate was the phasic discharge of some inspiratory or expiratory units converted to tonic activity.

These observations suggest that strong inhibitory processes serve to maintain the phasic firing pattern of respiratory units. These data also support the concept that active‐inhibitory phase‐switching mechanisms serve to define respiratory rhythmicity.
THE EFFECTS OF PIPEROXAN ON UPTAKE OF NORADRENALINE AND OVERFLOW OF TRANSMITTER IN THE ISOLATED BLOOD PERFUSED SPLEEN OF THE CAT
Authors: BLAKELEY A.G.H. , SUMMERS R.J.
Published: July 2012

The competitive α‐adrenoceptor blocking agent, piperoxan, in concentrations up to 2 × 10−4m, produced large dose‐dependent increases in transmitter overflow from the isolated blood perfused spleen of the cat following nerve stimulation at 10 hertz.

At concentrations greater than 2 × 10 −4 m, piperoxan produced a rise in perfusion pressure, a contraction of the splenic capsule, and a marked dose‐dependent decrease in transmitter overflow.

Phenoxybenzamine (10−4m) and desmethylimipramine (3 × 10−5m) produced further increases in transmitter overflow when added after piperoxan.

Piperoxan (5.8 to 6.6 × 10−6m) had no effect on the recovery of 3H in the venous blood following the close arterial infusion or injection of [3H]‐(−)−noradrenaline, indicating that the drug does not inhibit uptake of the amine.

Piperoxan produced dose‐dependent inhibition of responses of the splenic vasculature to close arterial injection of 1 μg of (—)‐noradrenaline but was much less effective at inhibiting responses to nerve stimulation. At 2 × 10 −6m piperoxan produced a considerable reduction of the response to injected noradrenaline but potentiated the response to nerve stimulation.

In isolated strips of cat splenic capsule, piperoxan produced a shift to the right of the dose‐response curve to noradrenaline with no change of the maximum response. There was no evidence of a postsynaptic sensitizing effect of the type observed in the rat vas deferens.
OCCURRENCE OF H,‐ AND H2‐HISTAMINE RECEPTORS IN THE GUINEA‐PIG GALL BLADDER in situ
Authors: IMPICCIATORE M.
Published: July 2012

Histamine has a dual action on the in situ gall bladder of the guinea‐pig: a spasmogenic and a relaxant effect mediated through Hr and H2‐receptor stimulation respectively.

The contracturant action, mimicked by 2‐(2‐aminoethyl) thiazole (a specific Hx‐receptor agonist), is blocked by mepyramine and the relaxation, mimicked by dimaprit (a specific H2‐receptor agonist), is inhibited by cimetidine.
SOME OBSERVATIONS ON THE DEVELOPMENT OF ADRENERGIC INNERVATION IN RABBIT INTESTINE
Authors: GULATI O.D. , PANCHAL D.I.
Published: July 2012

Stimulation of periarterial nerves to the ileum of 1 to 12 day old rabbits with supramaximal voltages and frequencies of 1, 2, 5, 10 and 20 Hz with square wave pulses of 2–5 ms duration for 30–40 s produced responses that were initially contractor. In the course of the first week, the responses changed from motor to inhibitory, the change occurring first at the highest rates of stimulation. By the 7th day of life, almost all responses were inhibitory.

The motor responses were potentiated by physostigmine and blocked by hyoscine suggesting that they were mediated by acetylcholine.

In preparations from rabbits older than 3 days, motor responses could be converted to inhibitory ones by prior exposure to noradrenaline (NA, 1 (ig/ml) for 20 min. This procedure also significantly increased the responses which were already inhibitory.

The ability of the ileum to take up NA increased with age. This uptake was blocked by cocaine.

The following explanations are possible: (a) changeover from cholinergic to adrenergic transmission in sympathetic fibres; (b) existence of ‘parasympathetic’ splanchnic nerves or a permanent cholinergic ‘sympathetic’ component of splanchnic nerves and (c) temporal delay in the development of adrenergic nerves (compared with cholinergic nerves) in the intestine.
RECIRCULATION OF PROSTACYCLIN (PGI2) IN THE DOG
Authors: DUSTING G.J. , MONCADA S. , VANE J.R.
Published: July 2012

The inactivation of prostacyclin (PGI2) in the circulation of anaesthetized dogs has been studied by the blood‐bathed organ bioassay technique.

Spiral strips of bovine coronary and rabbit coeliac or mesenteric artery detected concentrations of PGI2 of 2 to 5 ng/ml. These tissues were insensitive to concentrations at least 200 fold higher of 15‐oxo‐PGI2 and 6‐oxo‐PGFlat.

PGI2 assayed on bovine coronary artery, rabbit coeliac artery or rat stomach strip, had a half life in blood of 3.0 + 0.3 min, indicating non‐enzymatic degradation.

No disappearance could be detected by bovine coronary artery when PGI2 was infused across the lungs (0.1 to 0.5 (ig kg−1 min−1). However, PGI2 was partially inactivated in passage through vascular beds of hindquarters and liver.

Of PGI2 infused into the aorta 35 to 65% escaped inactivation in one complete circulation. Therefore, endogenous PGI2 released from the lungs may function as a circulating hormone.
β‐ADRENOCEPTOR BLOCKING DRUGS AND ISOPRENALINE: CENTRAL EFFECTS ON CARDIOVASCULAR PARAMETERS
Authors: COHEN Y. , LINDENBAUM A. , MIDOL‐MONNET MICHELE , PORQUET D. , WEPIERRE J.
Published: July 2012

The central hypotensive activity of (+)‐ and (—)‐propranolol (100 μg), pindolol (100 μg) and isoprenaline (1 and 4 μg) injected intracerebroventricularly (i.c.v.) was studied in rats anaesthetized with urethane and chloralose. Blood pressure, cardiac output and heart rate were measured; systolic stroke volume and peripheral vascular resistance were calculated.

(+)‐ and (—)‐Propranolol and pindolol induced a fall of blood pressure but (+)‐propranolol was less active. The heart rate was reduced more by (—)‐propranolol than by (+)‐propranolol or (—)‐pindolol. The decrease of systolic stroke volume was greater for (—)‐propranolol and pindolol than for (+)‐propranolol. Peripheral vascular resistance was reduced to the same level but with different time courses, (—)‐propranolol having a longer effect than (+)‐propranolol and pindolol.

Isoprenaline induced a hypotensive effect, while cardiac output and heart rate increased; the systolic stroke volume remained stable but peripheral vascular resistance was significantly decreased.

These results suggest that different central regulatory centres are involved in the control of cardiac function and peripheral vascular tone.
PHARMACOLOGICAL ASPECTS OF NEUROMUSCULAR TRANSMISSION IN THE ISOLATED DIAPHRAGM OF THE DYSTROPHIC (Rej 129) MOUSE
Authors: HARRIS J.B. , RIBCHESTER R.R.
Published: July 2012

Some aspects of the pharmacology of neuromuscular transmission have been studied in the isolated diaphragm of the normal and dystrophic mouse.

The effects of (+)‐tubocurarine and atropine on the indirectly elicited twitch responses of the dystrophic diaphragm were indistinguishable from normal.

Intracellular recording techniques revealed no significant differences between the rise time, time to half decay, frequency and amplitude of miniature endplate potentials (m.e.p.ps) recorded in dystrophic muscle fibres, compared to those recorded in normal muscle fibres.

Transmitter null potential, the size of the available store of transmitter, the probability of release of the transmitter, and the characteristics of endplate potentials (e.p.ps) of dystrophic muscle fibres did not differ from normal.

The quantum contents of e.p.ps generated in response to nerve stimulation of 0.1 to 100 Hz were consistently larger in dystrophic muscle fibres than in normal muscle fibres, but the differences were not statistically significant under the conditions of the experiment.
VENTILATORY DEPRESSION IN NAIVE AND TOLERANT RATS IN RELATION TO PLASMA MORPHINE CONCENTRATION
Authors: BOWEN S.R. , CARPENTER F.G. , SOWELL J.G.
Published: July 2012

The disappearance of morphine from specially formulated pellets containing 75 mg morphine base was measured for 10 days after they were implanted into adult rats; the morphine content decreased at a rate of 5 mg pellet daily.

From the 2nd to the 6th day of implantation the plasma morphine concentration increased but by the 10th day had declined to only one half the concentration found on day 6.

Six and 24 h after the pellets were removed from 6 day implanted animals the plasma concentration of morphine amounted to only one quarter to one sixth of the amount in the plasma, respectively, of animals with pellets intact.

The pulmonary minute volume of naive and implanted rats was depressed by morphine in proportion to the plasma morphine concentration. Less depression was produced by intravenous morphine in the implanted rats than in the naive animals; the greater morphine tolerance displayed by the implanted animals could be shown by the third day of implantation and appeared to be maintained to the 10th day.

The pulmonary minute volume of implanted rats on the 6th day was much less than the pulmonary minute volume of naive rats. Six and 24 h after the pellets were removed the pulmonary minute volume increased as the plasma morphine concentration decreased.

The effects on the pulmonary minute volume produced by the slow release of morphine from the implanted pellets was not changed by the development of tolerance while the effects of morphine produced by rapid injection were diminished by the development of tolerance; the different effects of morphine are accordingly linked to the mode of administration.

We conclude that the action of morphine on the pulmonary minute volume in tolerant rats following rapid injection is fundamentally different from its action following its slow release from implanted pellets, possibly due to differences in access to an undefined neuronal site.
SHAPE CHANGE OF BLOOD PLATELETS—A MODEL FOR CEREBRAL 5‐HYDROXYTRYPTAMINE RECEPTORS?
Authors: GRAF M. , PLETSCHER A.
Published: July 2012

In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein‐poor medium, tryptamine, 5‐hydroxytryptamine (5‐HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide.

The most potent antagonists of the 5‐HT‐induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity.

(‐f)‐Lysergic acid diethylamide ((+)‐LSD), psilocine and some N',N′‐dimethylated tryptamines acted as mixed agonist‐antagonists.

The compounds found to be agonists or mixed agonist‐antagonists on platelets have previously been shown to act also as 5‐HT agonists in the central nervous system (CNS).

With regard to 5‐HT antagonists, the 5‐HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5‐hydroxytryptaminergic innervation, but showed similarities to 5‐HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation.

It is concluded that platelets may be considered with caution as models for some, but not for all, 5‐HT receptors in the CNS.
THE CHARACTERISTICS OF [3H]‐CLONIDINE BINDING TO ANα‐ADRENOCEPTOR IN MEMBRANES FROM GUINEA‐PIG KIDNEY
Authors: JARROTT B. , LOUIS W.J. , SUMMERS R.J.
Published: July 2012

[3H]‐clonidine binds to membranes prepared from guinea‐pig kidney.

At 25°C the binding is rapid and saturable.

Scatchard analysis of the binding data showed that the Kd for [3H]‐clonidine binding in kidney membranes is 8.54 nM and the density of binding sites 12.5 pmol/g wet wt. tissue.

Hill plots of the binding data showed that there were no cooperative site interactions associated with binding.

[3H]‐clonidine binding could be displaced by drugs, the most potent being drugs with a high affinity for the α‐adrenoceptor. The neuroleptic drugs (+)‐butaclamol, ds‐clopenthixol and ds‐flupen‐thixol at high concentration also displaced [3H]‐clonidine binding.

Drugs acting as agonists or antagonists of β‐adrenoceptors, histamine receptors, acetylcholine receptors as well as prostaglandins E1 E2, Flα and F2α, angiotensin II, arginine vasopressin, naloxone, nalorphine and pargyline had little effect on binding.

It is likely that the binding site labelled by [3H]‐clonidine in guinea‐pig kidney membranes is an α‐adrenoceptor similar in some pharmacological aspects to an a2‐adrenoceptor.
ASSESSMENT OF THE EFFECTS OF VASOACTIVE INTESTINAL PEPTIDE (VIP) ON BLOOD FLOW THROUGH AND SALIVATION OF THE DOG SALIVARY GLAND IN COMPARISON WITH THOSE OF SECRETIN, GLUCAGON AND ACETYLCHOLINE
Authors: SHIMIZU T. , TAIRA N.
Published: July 2012

The vascular bed of the submandibular gland in situ was perfused with blood through the glandular artery at a constant pressure in anaesthetized dogs. All drugs were administered intra‐arterially.

Vasoactive intestinal peptide (VIP), secretin and acetylcholine produced a dose‐dependent increase in blood flow through the artery (vasodilatation) but glucagon was almost ineffective.

Dose‐blood flow response curves for VIP and secretin were parallel, and VIP was about 100 times as potent as secretin on a molar basis. Dose‐blood flow response curves for acetylcholine were flatter than those for VIP and secretin. Acetylcholine was approximately as potent as secretin on a molar basis.

No tachyphylaxis developed to the vasodilator action of VIP.

The vasodilator responses to VIP and to electrical stimulation of the chordolingual nerve were scarcely modified by (—)‐hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine.

VIP, secretin and glucagon were ineffective in eliciting salivary secretion.

The possibility that VIP is released from parasympathetic vasodilator nerves and mediates the atropine‐resistant vasodilatation in the dog submandibular gland is discussed.
THYROTROPHIN RELEASING HORMONE STIMULATES RELEASE OF [3H]‐DOPAMINE FROM SLICES OF RAT NUCLEUS ACCUMBENS in vitro
Authors: KERWIN R.W. , PYCOCK C.J.
Published: July 2012

Thyrotrophin releasing hormone (TRH) (25 to 100 μm) was found to stimulate the efflux of [3H]‐dopamine from small slices of rat nucleus accumbens, but not from similar slices of rat caudate nucleus. Uptake inhibition was not responsible for this action, since at 10 and 50 μm TRH had no effect on the ability of small slices of nucleus accumbens to accumulate radioactivity when incubated with 10−7 m [3H]‐dopamine. In addition the hormone had no effect on basal or dopamine‐stimulated adenylate cyclase, nor did it displace [3H]‐spiperone binding, in membrane preparations from nucleus accumbens.
OUABAIN RECEPTOR BINDING OF HYDROXYPROGESTERONE DERIVATIVES
Authors: CHOW EDWIN , KIM RYUNG‐SOON SONG , LABELLA FRANK S. , QUEEN GARY
Published: July 2012

A specific and sensitive radioreceptor assay has been devised which is based on high affinity, saturable binding of 9 nm [3H]‐ouabain to the total particulate fraction isolated from dog heart. Ouabain and other cardiac glycosides, including the aglycones, were about equipotent in their ability to displace [3H]‐ouabain from its receptor, the IC50s ranging from 10 to 30 nm.

The only other substances found to compete significantly in the assay were derivatives of hydroxy‐progesterone having a 17α‐acetate substituent: chlormadinone acetate, megestrol acetate, cyproterone acetate and medroxyprogesterone acetate, with IC50s of 2, 7.4, 9 and 21 μm, respectively. Prednisolone‐3,20‐bisguanyl‐hydrazone, reported to have inotropic activity, gave an IC50 of 6.4 μm. Cyproterone‐17α‐OH was less active (IC50 90 μm) than cyproterone‐17α‐acetate.

A large number of peptide and protein hormones, steroid hormones and their metabolites, amines, and drugs were inactive.
THE ORAL ACTIVITY OF Δ′‐TETRAHYDROCANNABINOL AND ITS DEPENDENCE ON PROSTAGLANDIN E2
Authors: FAIRBAIRN J.W. , PICKENS JOAN T.
Published: July 2012

Δ′‐trans‐Tetrahydrocannabinol (THC) is more active orally in mice than previously thought, as cataleptic responses occur at doses from 0.06mg/kg upwards, with peak activity at 2 to 4 h after dosing. These doses and peaks correspond well with the effects in man.

Comparison with chlorpromazine in mice shows that chlorpromazine and THC are equipotent as cataleptics during the first 2 h after dosing; thereafter the THC activity increases to a peak when it is 5.67 times as active as chlorpromazine.

The cataleptic effect of THC is abolished by aspirin, indomethacin, diflunisal and phenylbutazone which inhibit the biosynthesis of prostaglandins and is restored by exogenous prostaglandin E2 (PGE2) but not PGE1 and PGF2. This suggests that the effect of THC depends upon the presence of PGE2.

In contrast, the cataleptic effect of chlorpromazine is not affected by pretreatment with aspirin.

THC is very much less active intraperitoneally than orally; our results suggest this is not due to poor absorption or extraction into fat depots.

Cannabidiol has no cataleptic effect.
TEMPERATURE AND INHIBITORY JUNCTIONAL TRANSMISSION IN GUINEA‐PIG ILEUM
Authors: LANG RICHARD J.
Published: July 2012

The effects of temperature on the inhibitory junctional potential (i.j.p.) and the electrotonic potential, recorded in the circular smooth muscle of the guinea‐pig ileum, were studied with intracellular microelectrodes. The amplitude and time course of the i.j.p. were both dependent on the ambient temperature, the i.j.p. becoming smaller and more prolonged as the temperature was lowered. In contrast, the electrotonic potential was not much affected by temperature. The atropine‐resistant ‘late’ depolarization was also dependent on temperature. These results are consistent with the mechanism of release, of the nonadrenergic noncholinergic inhibitory transmitter, being sensitive to temperature and with the inhibitory conductance change, underlying the i.j.p., being long compared to the membrane time constant of the circular smooth muscle.
INHIBITION OF GUINEA‐PIG LYMPHOCYTE ACTIVATION BY HISTAMINE AND HISTAMINE ANALOGUES
Authors: BEETS J.L. , DALE M. MAUREEN
Published: July 2012

The incorporation of [3H]‐thymidine into guinea‐pig lymphocytes stimulated by a plant lectin (concanavalin A), soluble antigen (tuberculin (P.P.D.)) and syngeneic hepatoma cells, was partially inhibited (50%) by histamine in vitro.

The effect of histamine on both mitogen and antigen dose‐response curves suggests a non‐competitive, probably physiological antagonism.

The inhibitory dose range of histamine lay between 10 nm and 30 μm with an ID50 of approximately 400 nm.

The potency order for histamine analogues for the inhibition of lymphocyte activation was histamine ≥ 4‐methylhistamine > 2‐methylhistamine > 3‐methylhistamine. This is in accord with the mediation of the response through an H2‐receptor.

H2‐receptor antagonists reversed the inhibitory effect of histamine in a dose‐related manner, but both metiamide and burimamide, in high concentrations, augmented lymphocyte activation in their own right. This precluded the determination of affinity constants and made it impossible to state with certainty that the inhibition of lymphocyte activation by histamine was mediated by an H2‐receptor.
ACTIONS OF PROSTAGLANDIN PRECURSORS AND OTHER UNSATURATED FATTY ACIDS ON CONDUCTION TIME AND REFRACTORY PERIOD IN THE CAT HEART in situ
Authors: BAYER B.‐L. , FÖRSTER W.
Published: July 2012

The effect of arachidonic, dihomo‐γ‐linolenic, linoleic, α‐linolenic and oleic acid, given by intravenous infusion, on conduction time and functional refractory period have been studied in the cat heart in situ.

The prostaglandin precursors, arachidonic acid and dihomo‐γ‐linolenic acid, prolonged the conduction time and the functional refractory period. Linoleic acid was also effective but to a lesser degree. α‐Linolenic acid and oleic acid showed no or only a weak effect in this respect.

Pretreatment with indomethacin diminished or abolished the actions of the three effective fatty acids but not those of prostaglandin E2.

The results suggest that the effects of prostaglandin precursors on conduction time and refractory period are responsible for their antiarrhythmic effectiveness and that these effects are attributable to their endogenous conversion into prostaglandins.
THE EFFECTS OF H1‐ AND H2‐RECEPTOR AGONISTS AND ANTAGONISTS ON TOTAL LUNG RESISTANCE, DYNAMIC LUNG COMPLIANCE AND IRRITANT RECEPTOR DISCHARGE IN THE ANAESTHETIZED DOG
Authors: DIXON M. , JACKSON D.M. , RICHARDS I.M.
Published: July 2012

The effects of histamine and 4 methylhistamine (i.v.) alone, and in the presence of chlorpheniramine or cimetidine, on total lung resistance (RL), dynamic lung compliance (Cdyn) and irritant receptor activity have been studied in dogs anaesthetized with chloralose.

Histamine produced dose‐related increases in RL and irritant receptor activity with associated falls in Cdyn which were blocked by chlorpheniramine but unaffected by cimetidine.

4 Methylhistamine produced small insignificant changes in R1 and Cdyn and small significant increases in irritant receptor activity which were reduced with chlorpheniramine but unaffected by cimetidine.

The results suggest that histamine increases irritant receptor activity, either directly or indirectly, via H1‐receptors.
DECREASED BINDING OF DRUGS AND DYES TO PLASMA PROTEINS FROM RATS WITH ACUTE RENAL FAILURE: EFFECTS OF URETER LIGATION AND INTRAMUSCULAR INJECTION OF GLYCEROL
Authors: BOWMER C.J. , LINDUP W.E.
Published: July 2012

The decreased binding of drugs and dyes to plasma proteins from male and female rats with acute renal failure has been investigated using equilibrium dialysis at 37°C.

Acute renal failure induced by bilateral ligation of the ureters produced a greater than threefold increase in the unbound fraction of o‐methyl red relative to normal rat plasma. Unbound dye concentration in plasma from sham‐operated control rats was also significantly increased but to a lesser extent.

Glycerol‐induced acute renal failure produced a significant increase in the unbound fractions of o‐methyl red, methyl orange, bromocresol green (BCG), 2‐(4′‐hydroxybenzeneazo) benzoic acid (HABA), phenytoin and salicylic acid. A marginally significant increase in unbound warfarin concentration was observed.

Glycerol‐induced renal failure had no effect on total plasma protein concentration and experiments with o‐methyl red and salicylic acid indicated that a direct effect of glycerol was not responsible for the diminution of binding.

Glycerol‐induced acute renal failure, which produced decreases in drug and dye binding similar to those reported for human uraemic plasma, provides a convenient non‐surgical animal model for the investigation of this phenomenon.
ON THE DISTRIBUTION OF [MET5]‐ AND [LEU5]‐ENKEPHALINS IN THE BRAIN OF THE RAT, GUINEA‐PIG AND CALF
Authors: Di GIULIO A.M. , MAJANE E.M. , YANG H.‐Y.T.
Published: July 2012

By means of a highly sensitive radioimmunoassay, the content of [met5]‐enkephalin (ME) and [leu5]‐enkephalin (LE) was measured in various regions of the rat, guinea‐pig and calf brain. Provisions were made to differentiate ME from LE by the use of cyanogen bromide (CNBr) to destroy methionine, the carboxy terminal amino acid in the ME sequence. This allows for correction of possible errors due to the cross‐reactivity of the ME to the LE antiserum. Evidence is presented to demonstrate that the specific radioimmunoassay combined with the CNBr technique is a valid method to measure LE and ME content in crude tissue extracts.

In all the species studied, enkephalins appeared to be highly concentrated in the striatum and hypothalamus while very low amounts were found in the cerebellum and hippocampus.

Although the ratio between ME and LE content varied from area to area, the ME content in every region of the rat, guinea‐pig and calf brain was more than 4 fold greater than that of LE.
ACTION OF HISTAMINE RECEPTOR AGONISTS AND ANTAGONISTS ON THE RAT UTERUS
Authors: BERTACCINI G. , MOLINA E. , VITALI T. , ZAPPIA L.
Published: July 2012

Histamine and a series of compounds acting selectively on Hr and H2‐receptors were tested on the isolated oestrous uterus of the rat.

Histamine had a dose‐dependent inhibitory effect on the contractions elicited by acetylcholine. This action was unaffected by H1‐blockers but was competitively inhibited by H2‐blockers. The H1‐selective agonist, 2‐(2‐aminoethyl)thiazole was ineffective at doses 100 times greater than those of histamine. Conversely, all the H2‐agonists showed activity in the order of potency: N'‐methylhistamine > histamine > N'‐N'‐dimethylhistamine > 5‐methylhistamine > 5‐methyl‐N'‐methylhistamine. Among the non‐imidazole compounds, dimaprit had an activity identical to that of histamine, but all the dimaprit‐like compounds showed negligible activity.

The data obtained suggest that in the rat uterus, (a) the activation of H2‐receptors is responsible for the inhibitory effect of histamine and its analogues; (b) the integrity of the histamine molecule seems to be less crucial than that of the dimaprit molecule for the maintenance of the H2‐activity, since changes in its structure modify but do not abolish the biological activity as they do in the case of dimaprit; (c) the order of activity of the various H2‐receptor agonists is different from that observed in other tissues.
EVIDENCE THAT PROTEASE INHIBITORS REDUCE THE DEGRADATION OF PARATHYROID HORMONE AND CALCITONIN INJECTED SUBCUTANEOUSLY
Authors: PARSONS J.A. , RAFFERTY B. , STEVENSON R.W. , ZANELLI JOAN M.
Published: July 2012

Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH).

Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia.

The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h.

Of other protease inhibitors studied, e‐aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine.

By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously.

Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered.

The two protease inhibitors, e‐aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site.

It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.
AN ELECTROPHYSIOLOGICAL ANALYSIS OF THE EFFECTS OF MORPHINE ON THE CALCIUM DEPENDENCE OF NEUROMUSCULAR TRANSMISSION IN THE MOUSE VAS DEFERENS
Authors: BENNETT M.R. , LAVIDIS N.A.
Published: July 2012

The effects of morphine on the Ca‐dependence of the synaptic potential amplitude in the mouse vas deferens have been determined.

The synaptic potential increased with a power factor of 2.4 for [Ca]o between 0.7 mm and 1.8 mm. Morphine (40 nm) decreased the synaptic potential, without altering the second power relationship between the synaptic potential and [Ca]o.

Morphine reversed the depression in the synaptic potential which develops during a short high‐frequency (10 Hz) train of impulses to facilitation. Consequently the synaptic potential beyond the tenth impulse was unaffected by morphine.

Morphine did not alter the facilitation of the synaptic potential which develops during a short low‐frequency (≤2 Hz) train of impulses in normal [Ca]o. Consequently morphine decreased the synaptic potential for each impulse by about the same percentage amount.

Morphine increased the small facilitation in the synaptic potential which occurs during a short low‐frequency (≤2 Hz) train of impulses in high [Ca]o. This facilitation approximated the predictions based on the assumption that each impulse leaves residual Ca ions bound to receptors involved in transmitter release from the nerve terminal.
ADVERSE EFFECTS OF ARTIFICIAL BUFFERS ON CONTRACTILE RESPONSES OF ARTERIAL AND VENOUS SMOOTH MUSCLE
Authors: ALTURA B.M. , ALTURA B.T. , CARELLA A. , TURLAPATY P.D.M.V.
Published: July 2012

In vitro studies were undertaken on rat aortic strips and portal vein segments in order to determine whether or not several commonly used artificial buffers, i.e., tris(hydroxymethyl) aminomethane (Tris), N‐2‐hydroxyethylpiperazine‐N′‐2‐ethanesulphonic acid (HEPES), morpholine propanesulphonic acid (MOPS), N, N bis(2‐hydroxyethyl) glycine (BICINE) and 1,4‐piperazinediethanesulphonic acid (PIPES), can exert direct actions on vascular smooth muscle.

All artificial buffers used in 5 mm concentrations were found to inhibit development of spontaneous mechanical activity.

Tris, HEPES, MOPS, BICINE and PIPES markedly attenuated contractions induced by adrenaline, angiotensin and KCl. The fast phase components of the agonist‐induced contractions were either obliterated or reduced in the presence of the artificial buffers. The sustained slow phase components were greatly reduced and retarded by the artificial buffers.

The relative order of artificial buffer potency (i.e., from 100% to 14% inhibition) seems to depend upon the agonist and type of smooth muscle.

All of these inhibitory effects were reversible, since normal contractile responses and spontaneous mechanical activity could be obtained by simply reincubating the smooth muscles in Krebs‐Ringer bicarbonate buffer.

A variety of pharmacological antagonists failed to mimic or affect the inhibitory effects of Tris, HEPES, MOPS, PIPES and BICINE.

These data show that five of the most commonly used artificial buffers, to study muscles in vitro, exert adverse effects on contractility of arterial and venous smooth muscle.
3,4‐DIHYDROXYPHENYLACETIC ACID (DOPAC) AND THE RAT MESOLIMBIC DOPAMINERGIC PATHWAY: DRUG EFFECTS AND EVIDENCE FOR SOMATODENDRITIC MECHANISMS
Authors: BEART P.M. , GUNDLACH A.L.
Published: July 2012

Drug effects on dopamine catabolism of the mesolimbic dopaminergic pathway have been investigated using a sensitive radioenzymatic assay for 3,4‐dihydroxyphenylacetic acid (DOPAC).

Turnover of DOPAC was less rapid in the ventral tegmentum (containing somata and dendrites) than in the nucleus accumbens (containing nerve terminals): 9 and 115 ng g−1 min−1 for ventral tegmentum and nucleus accumbens respectively.

Reserpine (5 mg/kg, 1 h) elevated DOPAC concentration to a greater extent in ventral tegmentum than in nucleus accumbens.

Neuroleptic drugs elevated DOPAC levels in ventral tegmentum and nucleus accumbens. Thioridazine, sulpiride and clozapine, thought to act preferentially on the mesolimbic system, caused a similar elevation in both brain regions.

γ‐Butyrolactone (750 mg/kg) caused a significant decrease in the DOPAC concentration in ventral tegmentum after 0.5 and 1 h, while DOPAC levels in nucleus accumbens were not significantly altered at these time intervals.

Similarities exist between the dopamine catabolism in somatodendritic and nerve terminal regions of mesolimbic dopaminergic neurones in the response to neuroleptic drugs, but differences in catabolism are evident following certain pharmacological treatments such as reserpine and γ‐butyrolactone.

Dopamine release occurs in the somatodendritic region of mesolimbic dopaminergic neurones and release sites may be dendritic as has been found for nigrostriatal dopaminergic neurones.
NICOTINE INHIBITS HYPOXIA‐ AND ARACHIDONATE‐INDUCED RELEASE OF PROSTACYCLIN‐LIKE ACTIVITY IN RABBIT HEARTS
Authors: WENNMALM ÅKE
Published: July 2012

Rabbit hearts were perfused by the Langendorff technique and the interstitial effluent content of platelet anti‐aggregatory activity (prostacyclin‐like activity) was assayed at regular intervals.

Perfusion was performed with a solution containing 5% C02 in O2. At regular intervals it was changed to a solution containing 12% O2 and 5% CO2 in N2. Alternatively, perfusion with 5% CO2 in O2 was maintained during the entire experiment and sodium arachidonate was infused (5 to 15 μg/min) at intervals. Under the basal conditions no efflux of prostacyclin‐like activity was observed in the interstitial cardiac effluent, but both perfusion with a hypoxic solution and infusion of arachidonate induced such release.

Nicotine (5 × 10−5 m) in the solution perfusing the heart markedly inhibited the efflux of prostacyclin‐like activity into the cardiac interstitial effluent, induced by hypoxia or by infusion of arachidonate.

It is suggested that nicotine counteracts the formation of prostacyclin‐like activity in the rabbit heart by interfering with the enzymatic conversion of arachidonate to prostacyclin.
RELEASE OF PROSTAGLANDIN E FROM THE ISOLATED URINARY BLADDER OF THE GUINEA‐PIG
Authors: ALKONDON M. , GANGULY D.K.
Published: July 2012

Release of prostaglandin E (PGE) from guinea‐pig urinary bladder in vitro has been demonstrated both in the resting state and during electrical stimulation.

The electrically evoked release of PGE was significantly higher than the resting release and was frequency‐dependent.

The released substance was characterized as PGE pharmacologically by (a) blockade of its response by SC‐19220 on guinea‐pig ileum, (b) reduction of the amount of the released substance by indomethacin and (c) the inhibitory effect of the released substance on adrenergic neurotransmission in guinea‐pig vas deferens.

The prostaglandin seemed to originate from the muscle since tetrodotoxin treatment did not abolish the release during direct muscle stimulation; however, concomitant release from neuronal tissue could not be excluded in the present experiments.

Indomethacin failed to inhibit the mechanical responses of the bladder to transmural stimulation.

The present experiments suggest that PGE is not involved in mediating the non‐cholinergic non‐adrenergic neurotransmission in the guinea‐pig urinary bladder.
A COMPARISON OF CINOBUFOTENINE (THE QUATERNARY DERIVATIVE OF 5‐HT) AND SOME RELATED COMPOUNDS WITH CORYNEINE (THE QUATERNARY DERIVATIVE OF DOPAMINE) ON THE FROG RECTUS, GUINEA‐PIG ILEUM AND RAT FUNDUS STRIP PREPARATIONS
Authors: BARLOW R.B. , BURSTON K.N.
Published: July 2012

Coryneine is 2.7 times as active as cinobufotenine on the frog rectus but on the guinea‐pig ileum cinobufotenine is 1.5 times as active as coryneine. Cinobufotenine is a potent stimulant of parasympathetic ganglia and its effects are competitively antagonized by hexamethonium.

The effects of pH on activity relative to a standard whose ionisation is constant (Me4N+ or the trimethylammonium analogue of tryptamine) are consistent with the phenate form being weaker than the phenolic form but the changes are smaller than with coryneine because cinobufotenine is a weaker acid.

The hydroxyl group makes a large contribution to activity. Cinobufotenine is 9 times as active as the analogue without a hydroxyl on the frog rectus and 12 times as active as it on the ileum. The 5‐methoxy analogue is an antagonist on the frog rectus and a very weak partial agonist on the ileum.

Cinobufotenine and the quaternary derivative of tryptamine have less than one‐thousandth of the activity of 5‐hydroxytryptamine on the rat fundus strip.