bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECTS OF CERTAIN MUSCARINIC ANTAGONISTS ON THE ACTIONS OF ANTICHOLINESTERASES ON CAT SKELETAL MUSCLE
Authors: BRIMBLECOMBE R. W. , FRENCH MARY C. , WEBB SANDRA N.
Published: July 2012

The effects of some muscarinic antagonists, namely, N‐ethyl‐2‐pyrrolidylmethyl‐cyclopentylphenyl glycollate (PMCG), N‐methyl‐4‐piperidyl‐phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4′‐N‐methyl‐piperidyl‐l‐phenyl‐cyclopentane carboxylate (G3063) on organ o‐phosphate (sarin, soman)‐ and carbamate (neostigmine)‐induced twitch augmentation have been studied in cat soleus muscle.

The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function.

The muscarinic antagonists studied were capable of preventing or reversing sarin‐, soman‐ or neostigmine‐induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle.

The protective action of these muscarinic antagonists is dose‐dependent but independent of known antagonist actions at muscarinic receptors.

The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action.
SENSITIVITY OF MOUSE VAS DEFERENS TO NEUROTRANSMITTERS: CHANGES AFTER MORPHINE TREATMENT
Authors: CONTRERAS ENRIQUE , MARTI M. CRISTINA
Published: July 2012

The pharmacological responses of the isolated vas deferens of the mouse were investigated after acute and chronic treatment with morphine.

The addition of morphine to the bath did not alter the responses of the vas deferens to exogenous noradrenaline, adrenaline or dopamine.

Low doses of morphine depressed the responses to acetylcholine. Very high concentrations of the opioid (8.5 × 10−4m) completely abolished, in about 50% of the preparations, the responses to exogenous acetylcholine, while in the other 50% a potentiation of the responses to low concentrations of acetylcholine was observed.

The vas deferens of mice chronically treated with morphine showed increased sensitivity to exogenous noradrenaline, but decreased sensitivity to acetylcholine.

A fresh amount of morphine added to the bath enhanced the responses of morphine‐tolerant preparations to noradrenaline but not to dopamine or acetylcholine. The specificity of this phenomenon was demonstrated by the use of pentobarbitone instead of the opioid.

These results are in agreement with the theory that tolerance could result from a form of disuse supersensitivity.
ACTION OF PROSTAGLANDIN DEHYDROGENASE INHIBITORS ON PROSTAGLANDIN UPTAKE IN RAT ISOLATED LUNG
Authors: BAKHLE Y.S.
Published: July 2012

The effects of some inhibitors of 15‐hydroxy‐prostaglandin dehydrogenase (PGDH) have been studied on the inactivation of prostaglandin E2 (PGE2) and 16, 16‐dimethyl PGE2 in rat isolated lung.

Bioassay was used to show that the inactivation of PGE2 and its methyl analogue, was inhibited by frusemide (10−3m), N‐ethyl maleimide (10−5m) and 5, 5′‐dithio‐bis‐2‐nitro‐benzoic acid (10−2m), but not by caffeine (2.5 × 10−3m).

The efflux of radioactivity from lung following injection of [14C]‐PGE2 was faster in lungs treated with frusemide, N‐ethyl maleimide or bromcresol green, than in untreated lungs.

Caffeine (10−3, 10−2m) did not change the rate of 14C‐efflux from lungs following injection of [14C]‐PGE2.

From these results it is concluded that those PGDH inhibitors that prevented prostaglandin inactivation in isolated lungs did so by inhibiting uptake of prostaglandin rather than by inhibiting PGDH.
THE EFFECTS OF OPIOID DRUGS AND OF LITHIUM ON STEROIDOGENESIS IN RAT ADRENAL CELL SUSPENSIONS
Authors: GIBSON A. , GINSBURG M. , HALL M. , HART S.L.
Published: July 2012

The effects of opioid drugs and of Na+ replacement on steroidogenesis in rat adrenal cell suspensions were investigated.

In medium containing normal Na+ (156 mm), opioid antagonists but not opioid agonists reduced the steroidogenic response to adrenocorticotrophic hormone1–24. (ACTH1–24) but not to dibutyryl adenosine 3′,5′ cyclic monophosphate (db cyclic AMP).

Replacement of 50% Na+ in the medium by choline had no effect on steroidogenesis, but further reductions in Na+ content reduced the steroidogenic activity of both ACTH1–24 and db cyclic AMP.

In 50% Na+ medium both opioid agonists and antagonists inhibited ACTH1–24 induced steroidogenesis.

Addition of therapeutic concentrations of lithium to otherwise normal medium inhibited the steroidogenic response to ACTH1–24 but not to db cyclic AMP.

The selective inhibition of ACTH1–24‐induced steroidogenesis by opioid drugs suggests some similarity between the opioid and ACTH receptors.

The relevance of the potent inhibitory effect of lithium to its therapeutic actions is discussed.
THE ACTION OF MICROELECTROPHORETICALLY APPLIED (3,4‐DIHYDROXY‐PHENYLAMINO)‐2‐IMIDAZOLINE (DPI) ON SINGLE CORTICAL NEURONES
Authors: BEVAN P. , BRADSHAW C.M. , PUN R.Y.K. , SLATER N.T. , SZABADI E.
Published: July 2012

The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4‐dihydroxy‐phenylamino)‐2‐imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane.

DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses.

In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine.

The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected.

The α‐adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected.

It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by α‐adrenoceptors.
DRUG‐INDUCED CHANGES IN THE FORMATION, STORAGE AND METABOLISM OF TYRAMINE IN THE MOUSE
Authors: JUORIO A.V.
Published: July 2012

The endogenous concentrations of p‐ and m‐tyramine in the mouse striatum were determined by a mass spectrometric integrated ion current technique and concentrations were 21.3 and 6.1 ng/g, respectively.

The present results further confirm that the administration of antipsychotic drugs (chlorpromazine, haloperidol, spiroperidol, α‐flupenthixol and (+)‐butaclamol) reduces p‐tyramine concentrations in the mouse striatum. In contrast, striatal m‐tyramine showed a tendency to increase, although only in the cases of haloperidol and (+)‐butaclamol were the differences statistically significant.

Administration of antipsychotic drugs to mice pretreated with tranylcypromine or clorgyline produced a significant reduction in striatal p‐tyramine when compared with the concentrations obtained in mice given a monoamine oxidase inhibitor. These results suggest that antipsychotic drugs reduce striatal p‐tyramine formation. The moderate increases produced by monoamine oxidase inhibitors on striatal m‐tyramine were not significantly changed after the administration of an antipsychotic.

Drugs that reduce dopamine turnover (apomorphine, piribedil, lergotrile, α‐methyl‐p‐tyrosine) significantly increased the concentration of striatal p‐tyramine. No significant changes were observed in striatal m‐tyramine concentrations after apomorphine, piribedil or lergotrile; α‐methyl‐p‐tyrosine produced a reduction in its concentration.

Drugs that impair amine storage (reserpine, tetrabenazine, oxypertine) reduced striatal concentrations of p‐tyramine. The m‐tyramine concentrations were also reduced by reserpine or tetrabenazine.

It is possible that striatal tyramines act as modulators, or transmitters, and control the activity of dopaminergic neurones.
CONTRACTURES ELICITED BY TETRAETHYLAMMONIUM IN AVIAN MUSCLE TREATED WITH METHOHEXITONE
Authors: ELLIOTT R.C.
Published: July 2012

The chick biventer cervicis muscle immersed in methohexitone (8.8 × 10−5 m) responded to tetraethylammonium with contractures which were dose‐related. The ED50 for tetraethylammonium was 2.1 × 10−3 m.

In the absence of methohexitone, tetraethylammonium produced contractures only at much higher concentrations; these contractures were accompanied by fasciculations and neuromuscular block of the twitch fibres.

The contractures produced by tetraethylammonium in the presence of methohexitone were not reduced by exposure to botulinum toxin which eliminated all response of the muscle to indirect stimulation.

Tubocurarine (1.2 × 10−6 m) displaced the dose‐response curve for tetraethylammonium‐methohexitone‐induced contractures to the right. The dose‐ratio was 15.63 ± 1.98.

Physostigmine (1.8 × 10−6 m) potentiated the activity of tetraethylammonium‐methohexitone 3.26 or 3.84 fold, depending on the method of calculation used.

Physostigmine potentiated contractures elicited by indirect repetitive stimulation 4.8 to 6.0 fold more than it potentiated contractures due to tetraethylammonium‐methohexitone.

It is concluded that in the presence of methohexitone, tetraethylammonium produces contractures of the chick muscle by releasing acetylcholine but also by a direct agonist action on the cholinoceptor.
INVESTIGATION OF THE MECHANISM OF PROPRANOLOL‐INDUCED BRONCHOCONSTRICTION
Authors: MACLAGAN JENNIFER , NEY URSULA M.
Published: July 2012

Dose‐related increases in airways resistance (Raw) and decreases in dynamic lung compliance (Cdyn) were recorded in guinea‐pigs and rats following intravenous injection of propranolol and of the cardioselective β‐adrenoceptor blocking drugs, atenolol and practolol.

The bronchoconstriction reached a peak in 2 to 4 min and subsided within 15 min. Repeated injections caused identical responses in the airways.

The isomer (+)‐propranolol, which has only weak β‐adrenoceptor blocking activity, produced identical responses when given alone or when given after a dose of the racemate, sufficient to cause measurable β‐adrenoceptor blockade in the lungs.

After the initial bronchospasm had subsided, the β‐adrenoceptor blocking drugs and the isomer, (+)‐propranolol, produced potentiation of the bronchoconstrictor effects of 5‐hydroxytryptamine and histamine.

Both the bronchospasm and the potentiation occurred in adrenal demedullated rats.

The results indicate that the bronchoconstrictor effects of these drugs are unrelated to β‐adrenoceptor blockade in the airway smooth muscle.
STIMULATION AND INHIBITION OF THE SODIUM PUMP BY CARDIOACTIVE STEROIDS IN RELATION TO THEIR BINDING SITES AND THEIR INOTROPIC EFFECT ON GUINEA‐PIG ISOLATED ATRIA
Authors: GHYSEL‐BURTON JOSIANE , GODFRAIND T.
Published: July 2012

The actions of ouabain, ouabagenin and dihydroouabain on the contractility and on the ionic content have been investigated in left guinea‐pig atria stimulated at 3.3 Hz. The specific binding of ouabain and its displacement by the other cardenolides have been determined.

The action of either ouabain or ouabagenin on Na and K content was qualitatively different according to the concentration employed. Low doses evoked a reduction of Nai whereas high doses produced an increase. Dihydroouabain evoked only a Nai gain.

The increase of KCl concentration from 2.7 to 12 mm decreased Nai in untreated atria and displaced ouabain dose‐effect curves to the right.

ED50 values for the positive inotropic effect were lower than ED50 values for the inhibition of the pump and were not similarly affected by an increase in KCl concentration.

The specific binding of ouabain occurred at high and low affinity sites, related to Na pump stimulation and inhibition respectively.

The increase in KCl reduced the affinity of the two groups of sites for ouabain and increased the capacity of the high‐affinity sites whereas the capacity of the other sites remained unchanged.

The results confirm the existence of two specific binding sites for ouabain in guinea‐pig heart and suggest that the inhibition of the Na pump is not the only mechanism responsible for the positive inotropic effect of cardiac glycosides.
EFFECT OF 5‐HYDROXYTRYPTAMINE ON PROTEIN SYNTHESIS IN GASTROINTESTINAL AND OTHER TISSUES AND ON SERUM GASTRIN CONCENTRATIONS IN RATS
Authors: MAJUMDAR ADHIP P. NANDI , NAKHLA ATIF M.
Published: July 2012

The effect of 5‐hydroxytryptamine (5‐HT) on protein synthesis in the gastrointestinal tissues as well as in the liver, heart and brain was studied by measuring [3H]‐leucine incorporation into total tissue protein in vivo in rats.

A single injection of 5‐HT (10 mg/kg) produced a marked inhibition (45 to 65%) in protein synthesis in the stomach (oxyntic gland area), intestine (jejunum + ileum), colon and brain, but not in the liver and heart.

Dose‐ and time‐dependent studies of 5‐HT‐induced changes in protein synthesis in the stomach of fed rats revealed that the maximal inhibition of about 65% occurred 1 h after a dose of 12.5 mg/kg.

Animals deprived of food for 24 h differed from their fed counterparts only in the degree of responsiveness, in that a greater inhibition (75%) of [3H]‐leucine incorporation into total protein of the stomach was observed 30 min after 5‐HT injection.

Pretreatment of animals with methysergide (0.25 mg/kg) essentially abolished the 5‐HT‐mediated inhibition of protein synthesis in the stomach.

Serum gastrin concentration in fasted animals remained slightly elevated during the initial period of 5‐HT treatment (up to 1 h).

The results demonstrate that in certain tissues, 5‐HT markedly inhibits protein synthesis. The inhibition in protein synthesis in the gastrointestinal tract cannot be attributed to changes in the concentration of gastrin.
RELATIONSHIP BETWEEN ACCUMULATION, STORAGE AND OVERFLOW OF NORADRENALINE IN THE RAT SALIVARY GLAND AFTER CHRONIC TREATMENT WITH GUANETHIDINE
Authors: KHAN MOHAMMAD T. , WAKADE ARUN R.
Published: July 2012

The effect of guanethidine on the endogenous noradrenaline (NA) content, accumulation and overflow of [3H]‐noradrenaline ([3H]‐NA) in the rat salivary gland was examined at various times after drug administration.

Twenty‐four h after a single injection of guanethidine (1 or 10 mg/kg s.c), the respective values for the endogenous NA content and for the accumulation and overflow of [3H]‐NA were approximately 55, 85, 30%, and 15, 55, 10% of the controls.

Although [3H]‐NA accumulation had returned to control levels within 48 h after the dose of 10 mg/kg guanethidine, the overflow of [3H]‐NA evoked by electrical stimulation or excess potassium (K+) remained depressed.

After the low or the high dose of guanethidine, the NA content of the salivary gland was restored to about 50% of the normal value between 4 to 24 and 48 to 72 h, respectively.

The accumulation of [3H]‐NA was inhibited by about 75% by cocaine. The same degree of inhibition was obtained 4 h after 10 mg/kg guanethidine. In these experiments phenoxybenzamine did not reduce the residual (25%) uptake.

The reasons for differential rates of recovery of the endogenous NA content and the storage of [3H]‐NA after guanethidine are discussed.
EFFECTS OF β2‐ADRENOCEPTOR STIMULATION ON CARDIAC METABOLISM IN THE CONSCIOUS DOG
Authors: SHANAHAN E. ANNE , WAHLQVIST MARK L. , WILMSHURST ERROL G.
Published: July 2012

The effects of the β2‐adrenoceptor stimulant, salbutamol, on cardiac metabolism have been studied in conscious mongrel dogs. The potential effects of anaesthesia on the study of cardiac metabolism have been avoided by prior implantation of arterial (A) and coronary sinus (CS) catheters for blood sampling and a central venous catheter for infusion. Extraction of substrates for myocardial energy metabolism (CA—CS) was assessed 3 to 24 days post‐operatively. A 100 μg bolus of salbutamol was given followed by an infusion of 3 μg/min for 1 h.

Although heart rate increased significantly from 106 to 165 beats/min, fractional extraction of oxygen tended to fall from 84% to 77%. Thus an increase in coronary blood flow rather than in oxygen extraction must have maintained an oxygen supply commensurate with the salbutamol‐induced tachycardia.

Neither CA—CS glucose nor fractional glucose extraction altered significantly during salbutamol infusion despite increases in arterial concentration (CA) of glucose and arterial insulin immunoreactivity and a decrease in CA of free fatty acids (FFA). This suggests that an insulin‐antagonistic action accompanies the infusion of salbutamol.

The fractional extraction of lactate increased during salbutamol infusion. In part, this may have been a reflection of a decreased myocardial extraction of FFA with salbutamol in this model.
CARDIOVASCULAR RESPONSES PRODUCED BY THE INJECTION OF DOPAMINE INTO THE CEREBRAL VENTRICLES OF THE UNANAESTHETIZED DOG
Authors: LANG W.J. , WOODMAN O.L.
Published: July 2012

The injection of dopamine (100 to 500 μg) into the cerebral ventricles (i.c.v.) of 10 unanaesthetized dogs produced a dose‐dependent increase in arterial blood pressure and heart rate. The dogs licked, swallowed, sometimes vomited and became sedated.

Autonomic ganglion blockade with hexamethonium (10 mg/kg, i.v.) abolished cardiovascular responses to i.c.v. dopamine, indicating that dopamine was exerting its effect within the central nervous system.

The dopamine receptor antagonists, haloperidol (500 μg), chlorpromazine (200 μg) and ergometrine (500 μg), each given i.c.v., subsequently abolished the cardiovascular responses to dopamine.

Pretreatment with either the β‐adrenoceptor antagonist, propranolol (600 μg) or the α‐adrenoceptor antagonist, phentolamine (1 mg) given i.c.v. had no significant effect on the response to dopamine.

It is suggested that dopamine injected into the cerebral ventricles of the unanaesthetized dog causes hypertension and tachycardia by activating central dopamine receptors.
THE EFFECTS OF DISOPYRAMIDE PHOSPHATE ON EARLY POST‐CORONARY ARTERY LIGATION DYSRHYTHMIAS AND ON EPICARDIAL ST‐SEGMENT ELEVATION IN ANAESTHETIZED DOGS
Authors: MARSHALL R.J. , PARRATT J.R.
Published: July 2012

The antidysrhythmic, haemodynamic and metabolic effects of intravenously administered disopyramide phosphate (1 to 5 mg/kg) have been studied in greyhounds, anaesthetized with trichloroethylene.

In doses of 2.5 and 5.0 mg/kg, disopyramide significantly reduced the ventricular dysrhythmias that occur in the initial 30‐min period following acute coronary artery ligation. None of the disopyramide‐treated animals developed ventricular fibrillation.

The metabolic consequences of coronary artery ligation, assessed by local coronary venous sampling from the ischaemic area, were not modified by disopyramide except that K+ egress was prevented.

There was evidence for substantial disopyramide‐induced myocardial depression (decreased cardiac output and left ventricular dP/dtmax with elevated ventricular filling pressure and pulmonary oedema and shunting) and it is suggested that great care be taken when the drug is administered intravenously in conditions where cardiac function is already compromised. Disopyramide also reduced myocardial blood flow.

In chloralose‐anaesthetized mongrel dogs, disopyramide (2.5 mg/kg) significantly reduced the ST‐segment elevation (assessed from epicardial recordings) that resulted from short (3 min) coronary artery occlusions. This could indicate a reduction in the extent and severity of myocardial injury or simply reflect decreased K+ efflux (since locally administered K+ itself increased ST‐segment elevation).
THE EFFECT OF SOME GENERAL ANAESTHETICS ON THE SURFACE POTENTIAL OF LIPID MONOLAYERS
Authors: BANGHAM A.D. , MASON W.
Published: July 2012

This study sought to investigate the report by Ginsberg (1978) that 0.7 m ethanol brought about a +100 mV change (ΔΔV) in the surface potential of glyceryl monooleate (GMO) monolayers formed on KCl, although he predicted that a ΔΔV of −10 mV should have been found.

The effect of general anaesthetics such as n‐alkyl alcohols and pentobarbitone on surface potential (ΔV) and surface tension (γ) of lipid monolayers formed on 145 mm KCl from either glyceryl monooleate (GMO) or phosphatidyl choline (PC) was examined with an Americium‐241 air electrode assembly (ΔV) and a platinized platinum dipping plate and force balance (γ).

It was found that, as predicted by Ginsberg (1978), addition of 0.7 m ethanol to the aqueous phase bathing either PC or GMO monolayers brings about a negative‐going change in interfacial potential (ΔΔV).

The magnitude of ΔΔV is dependent in a linear fashion on ethanol concentration.

Longer chain length alcohols up to n‐decanol also bring about a negative going change in ΔΔV, and the dependence of ΔΔV on anaesthetic activity, with respect to increasing chain length of anaesthetic, is consistent with Traube's law.

Pentobarbitone added to the aqueous phase bathing the monolayer also elicits a negative ΔΔV, a finding which rules out the possibility of adsorption of the volatile alcohols to the measuring electrode.

The findings are discussed in terms of the proposition that increasing disorder in an array of fixed dipoles, such as might occur in a bilayer exposed to anaesthetic, would result in a lowering of the electrostatic barrier to the predominantly impermeable cation.
EFFECTS OF NORADRENALINE AND CARBACHOL ON TEMPERATURE REGULATION OF COLD‐STRESSED AND COLD‐ACCLIMATED RATS
Authors: POOLE S. , STEPHENSON J.D.
Published: July 2012

Noradrenaline (20 μg) and carbachol (1 μg) injected into the anterior hypothalamus of rats at an ambient temperature of 23°C evoked significant falls in core temperature and increases in tail temperature.

When rats were cold‐stressed (4°C for 90 min) or cold‐acclimated (4°C for 4 weeks) and the above amine injections repeated, only carbachol evoked significant falls in core temperature and neither amine increased tail temperature.

Central injections of noradrenaline and carbachol also evoked increases in plasma glucose concentrations but not plasma non‐esterified fatty acid (NEFA) concentrations in control, acutely cold‐stressed and cold‐acclimated rats.

Although concentrations of plasma glucose and blood lactate of rats were unaffected by cold exposure to 4°C for 1 to 28 days, glucose oxidation rate of both cold‐stressed and cold‐acclimated rats was significantly greater than in rats at 23°C. Concentrations of plasma NEFA were increased after 1 to 28 days of cold exposure.
THE RELATIONSHIP BETWEEN THE PHARMACOKINETICS, CHOLINESTERASE INHIBITION AND FACILITATION OF TWITCH TENSION OF THE QUATERNARY AMMONIUM ANTICHOLINESTERASE DRUGS, NEOSTIGMINE, PYRIDOSTIGMINE, EDROPHONIUM AND 3‐HYDROXYPHENYLTRIMETHYLAMMONIUM
Authors: BARBER H.E. , CALVEY T.N. , MUIR K.T.
Published: July 2012

The relationship between the concentration of drug in plasma, the inhibition of erythrocyte acetylcholinesterase and the facilitation of neuromuscular transmission has been studied in the rat after the administration of neostigmine, pyridostigmine, edrophonium and 3‐hydroxyphenyltrimethylammonium (3‐OH PTMA).

After the administration of neostigmine or pyridostigmine, acetylcholinesterase activity recovered only slowly due to the covalent nature of the inhibition. In contrast, recovery from the reversible inhibition caused by edrophonium or 3‐OH PTMA was rapid and showed a direct relationship to the plasma concentration of these drugs.

There was a statistically significant linear correlation between the logarithm of the plasma concentration of the drugs and the increase in the tibialis twitch tension.

The relationship between the inhibition of acetylcholinesterase and the facilitation of neuromuscular transmission was complex. When the enzyme was less than 85% inhibited no facilitation occurred. Between 85% and 98% inhibition, facilitation was linearly related to enzyme inhibition. Above 98% inhibition, facilitation was unrelated to inhibition of the enzyme.
THE EFFECT OF α‐ADRENOCEPTOR ANTAGONISTS AND METIAMIDE ON CLONIDINE‐INDUCED LOCOMOTOR STIMULATION IN THE INFANT RAT
Authors: NOMURA Y. , SEGAWA T.
Published: July 2012

Subcutaneous injections of clonidine (3.9 × 10−8 mol/kg to 3.9 × 10−6 mol/kg) produced forward locomotion and wall climbing in 7‐day‐old rats in a dose‐dependent manner.

The effect was reduced significantly by a preceding intraperitoneal injection of phentolamine (7.9 × 10−6 mol/kg), phenoxybenzamine (7.4 × 10−6 mol/kg), yohimbine (1.3 × 10−6 mol/kg) or piperoxan (7.4 × 10−6 mol/kg).

The pA2‐values of the antagonists to the clonidine‐induced locomotor hyperactivity were: 5.1 (phenoxybenzamine), 5.2 (phentolamine), 6.4 (yohimbine) and 6.0 (piperoxan).

Metiamide (2.5 × 10−4 mol/kg, 5.0 × 10−4 mol/kg and 1.0 × 10−3 mol/kg), a histamine H2‐receptor blocker, did not affect the clonidine‐induced locomotor stimulation.

It is suggested that the receptors which mediate clonidine‐induced locomotor stimulation could be α‐adrenoceptors but not histamine H2‐receptors in the central nervous system of the infant rat.
EFFECT OF GUANIDINE ON RELEASE OF NORADRENALINE FROM THE PERFUSED SPLEEN OF THE CAT
Authors: HIRSCH J. , KIRPEKAR S.M. , PRAT J.C.
Published: July 2012

Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected.

NA output was doubled at low concentrations (1 to 2 mm) of guanidine, but maximal effect was obtained at 4 mm. At 10 mm, spontaneous release was occasionally observed.

The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mm calcium‐Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mm, but maximum output was obtained at 2.5 mm.

Guanidine had no effect on the recovery of intra‐arterially infused NA.

The effects of guanidine and tetraethyl‐ammonium (TEA) on NA release at 5 Hz were additive.

Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz.

Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation.

It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding of calcium.
THE EFFECTS OF α‐ADRENOCEPTOR AGONISTS AND ANTAGONISTS ON RESPONSES OF TRANSMURALLY STIMULATED PROSTATIC AND EPIDIDYMAL PORTIONS OF THE ISOLATED VAS DEFERENS OF THE RAT
Authors: BROWN CHRISTINE M. , McGRATH J.C. , SUMMERS R.J.
Published: July 2012

The effects of α‐adrenoceptor agonists and antagonists on contractile responses of transmurally stimulated prostatic and epididymal portions of the rat isolated vas deferens were examined.

Responses to single stimuli consisted of two phases, the first predominant in the prostatic and the second in the epididymal portion. The first phase was resistant to α‐adrenoceptor antagonists but the second was reduced in a dose‐related manner in the order of potency prazosin > azapetine > phentolamine > labetalol > yohimbine.

Both phases of the response to a single stimulus were reduced by clonidine but only the first could be reliably restored by yohimbine.

Trains of transmural stimuli produced biphasic. responses, an early rapid component predominant in the prostatic and a slower secondary component predominant in the epididymal portion. The effects of α‐adrenoceptor antagonists on these responses were complex. Prazosin produced the most straightforward inhibition of responses with relative resistance of the early rapid component. Only yohimbine and phentolamine produced increases in responses which could be pre‐junctional in origin.

The α‐adrenoceptor agonists, oxymetazoline and clonidine, reduced while phenylephrine increased responses to trains of stimuli.

These results are discussed in relation to the nature of the innervation of rat vas deferens and the usefulness of the preparation in pharmacological tests for activity at α‐adrenoceptors.
TEMPERATURE COEFFICIENTS OF AFFINITY AND ENTROPIES OF ADSORPTION FOR ENANTIOMERIC PAIRS OF COMPOUNDS ACTING AT MUSCARINIC RECEPTORS IN THE GUINEA‐PIG ILEUM
Authors: BARLOW R.B. , BURSTON K.N.
Published: July 2012

The affinities of a series of enantiomeric pairs of esters of phenylcyclohexylglycollic acid, of a pair of esters of α‐methyltropic acid and of hyoscyamine methiodide have been measured for the muscarinic receptors of the guinea‐pig ileum at 30° and 37°C and estimates have been made of their free energies, enthalpies and entropies of adsorption.

With (−)‐S‐hyoscyamine methiodide the enthalpy of adsorption is negative whereas with the (+)‐R‐enantiomer it is positive.

With the esters of phenylcyclohexylglycollic acid the size of the onium group appears to be as important as the stereochemical configuration in determining entropy. Large onium groups appear to be associated with an increase in entropy though this can only be measured approximately because of the narrow range of temperature which can be used.
THE EFFECT OF THE AMINOSTEROID, ORG 6001, ON HYPOTHERMIA‐INDUCED VENTRICULAR FIBRILLATION IN THE CAT
Authors: KANE KATHLEEN A. , McDONALD FIONA M. , PARRATT J.R.
Published: July 2012

The effect of the antidysrhythmic aminosteroid, ORG 6001, on hypothermia‐induced ventricular fibrillation was investigated in cats anaesthetized with pentobarbitone.

ORG 6001 (total dose, 10 mg/kg, by intravenous injection) reduced both the incidence of fibrillation and the temperature at which it occurred. The number of animals that survived to 16°C was increased.

This protective effect of ORG 6001 could not be explained by changes in respiratory acidosis, plasma concentrations of sodium and potassium, or by changes in the action potential of excised hypothermic ventricular muscle. The hypothermia‐induced elevation of blood lactate was less in cats treated with the aminosteroid.

Over a limited temperature range, ORG 6001 prolonged the P wave and QRS duration and shortened the QTC interval. ST segment elevation was slightly reduced in the drug‐treated group. J deflections were observed but were not correlated with the development of fibrillation.

The onset of fibrillation was not considered to be due to temperature differences between the myocardium and arterial blood or between localized areas of the left ventricular wall.
COMPARISON OF THE EFFECTS OF A BENZOTRIAZINIUM IODIDE AND QUINIDINE ON GUINEA‐PIG HEART
Authors: FRENCH A.M. , SCOTT N.C.
Published: July 2012

The actions of 2‐H‐propyl‐4‐p‐tolylamino‐l,2,3‐benzotriazinium iodide (TnPBI) and quinidine were compared on guinea‐pig heart preparations.

Quinidine had negative inotropic and chronotropic effects on guinea‐pig isolated atria and on Langendorff hearts: TnPBI had negative inotropic and chronotropic effects on Langendorff hearts, but showed a positive inotropic effect on isolated atria at low dose levels.

Both quinidine and TnPBI increased the effective refractory period of guinea‐pig atrial preparations.

The effects of TnPBI on transmembrane action potentials indicated a mixed class I and class III action according to the classification of Vaughan Williams (1970).

These effects are discussed in relation to the antiarrhythmic actions of TnPBI.
CARDIOVASCULAR EFFECTS OF HYPERTONIC SODIUM CHLORIDE SOLUTIONS WHEN INJECTED INTO THE LIQUOR SPACE OF ANAESTHETIZED CATS
Authors: FELDBERG W. , WEI E.
Published: July 2012

In cats anaesthetized with chloralose, hyper‐ and hypotonic solutions were injected into the cisterna magna (in 0.5 ml) or into a lateral cerebral ventricle (in 0.2 to 0.3 ml), with aqueduct cannulated to prevent the injected solution from entering the subarachnoid space, and the effects on blood pressure and heart rate were examined.

Cisternal injections of hyper‐ and hypotonic solutions of NaCl (0.51 m and 0.05 m), glucose (1.03 m and 0.10 m), or sucrose (1.02 m and 0.10 m), as well as distilled water produced a rise in arterial blood pressure with tachycardias. Isotonic solutions of NaCl, glucose or sucrose were ineffective.

Ventricular injections of the hypertonic NaCl solution, also produced a pressor response with tachycardia as did an equally hypertonic solution of NaHC03 but the other solutions produced no circulatory effects when injected in this way.

The pressor responses and the tachycardias occurred after bilateral vagotomy and resulted from a sympathetic discharge which, on cisternal injection, originated from structures reached from the subarachnoid space, and on ventricular injection, from structures in the ventricular walls, probably in the hypothalamus.

The stimuli responsible for the discharge, were, on cisternal injection, the changes in osmolarity. and on ventricular injection, the sodium ions.
EFFECTS OF ARACHIDONIC ACID ON RAT GASTRIC ACID SECRETION IN RESPONSE TO DIFFERENT SECRETOGOGUES; INHIBITION OF THESE EFFECTS BY INDOMETHACIN
Authors: FRAME MADELINE H. , MAIN I. HARVEY M.
Published: July 2012

The effects of the prostaglandin precursor, arachidonic acid, and the non‐steroidal anti‐inflammatory drug, indomethacin, on gastric acid secretion were studied in the rat, in vivo and in vitro. Gastric mucosal blood flow was also measured in vivo.

Arachidonate produced significant inhibition of acid secretion stimulated by pentagastrin or histamine. It did not significantly affect dibutyryl cyclic adenosine 3′, 5′‐monophosphate (db cyclic AMP)‐induced acid secretion.

Inhibition of acid secretion by arachidonate was accompanied by a rise in the ratio of mucosal blood flow to acid secretion.

Indomethacin did not significantly alter histamine‐ or pentagastrin‐induced acid secretion.

In the presence of indomethacin, the inhibitory effect of arachidonate was significantly reduced.

These results provide evidence that the rat gastric mucosa is capable of synthesizing, from exogenous precursor, products of cyclo‐oxygenase which inhibit gastric acid secretion.
THE RELATIONSHIP BETWEEN NERVE TERMINAL ADENOSINE TRIPHOSPHATASES AND NEUROTRANSMITTER RELEASE: AS DETERMINED BY THE USE OF ANTIDEPRESSANT AND OTHER CNS‐ACTIVE DRUGS
Authors: GILBERT JOHN C. , WYLLIE MICHAEL G.
Published: July 2012

The role of adenosine triphosphatases (ATPases) in neurotransmitter release was studied using nerve terminals (synaptosomes) prepared from rat cerebral cortex as a model.

Amitriptyline, nortriptyline, protriptyline, desipramine and imipramine were found to inhibit ATPases at concentrations of 10−5 m and above. The drugs inhibited both the basal and electrically evoked release of acetylcholine (ACh) and noradrenaline (NA) at concentrations of 10−4 m and above.

At low concentrations of antidepressants (10−8 and 10−7 m) release of NA was enhanced but there was no effect on ACh release.

Other drugs which inhibit Na+, K+‐ATPase increased basal NA release as did drugs which inhibited vesicular Mg2+‐ATPase.

A model is proposed suggesting that transmitter release/re‐uptake depends on (1) active Na+, K+‐ATPase at the presynaptic membrane and (2) an active synaptic vesicular Mg2+‐ATPase.
THE EFFECTS OF VINCRISTINE ON PLATELET AGGREGATION STUDIED BY A FILTER LOOP TECHNIQUE IN THE RAT
Authors: BEE DENISE , LEACH ENID , MARTIN J.F. , SUGGETT A.J.
Published: July 2012

A method for measuring aggregation of platelets by adenosine diphosphate (ADP) is described using a filter inserted into the flowing aortic blood in the rat.

Repeated infusions of ADP resulted in a fall in the calculated aggregation index without significant changes in the platelet count.

Vincristine (0.05 mg/kg) intravenously caused significant inhibition of ADP‐induced platelet aggregation.

Infusion of ADP caused some peripheral vasodilatation though it is unlikely that this contributed to the effects seen to any great extent.
THE ISOLATED CIRCULAR MUSCLE LAYER OF THE VAS DEFERENS OF THE GUINEA‐PIG
Authors: ANSTEY MARY D. , BIRMINGHAM A.T.
Published: July 2012

A method is described for the removal of the outer longitudinal layer of muscle from the guinea‐pig isolated vas deferens. The remaining tube of circular muscle was perfused at constant flow for recording changes in pressure in response to transmural electrical stimulation or to drugs.

The response to transmural stimulation was a rise in perfusion pressure at frequencies of stimulation of 5 to 50 Hz for trains of 16 to 256 pulses. At some frequencies and train lengths a second rise in pressure (the after‐response) occurred after the cessation of the stimulus train.

Perfused vasa stripped of their longitudinal muscle did not develop longitudinal tension on electrical stimulation nor on intraluminal or extraluminal exposure to agonists.

Stripped perfused vasa gave concentration‐dependent pressure rises to noradrenaline but not to acetylcholine.

Responses to transmural stimulation and to noradrenaline were antagonized by thymoxamine. Cocaine or desmethylimipramine increased the duration of the after‐response to transmural stimulation. Reserpine pretreatment almost abolished the response and after‐response. The after‐response, but not the response, was increased by physostigmine and antagonized by atropine.

The results are discussed in relation to the known histochemical and electronmicroscopical demonstrations of dense noradrenergic and cholinergic populations of nerve terminals in the circular layer. It is suggested that mechanisms may exist for the separate control of the longitudinal and circular layers as a basis for propulsive activity.
α‐SYMPATHOMIMETIC AMINES AND CALCIUM‐MEDIATED ACTION POTENTIALS IN GUINEA‐PIG VENTRICULAR MUSCLE
Authors: LEDDA F. , MANTELLI L. , MUGELLI A.
Published: July 2012

The ability of amines, having α‐ or α‐ and β‐ adrenoceptor stimulating activity, to restore excitability and contractility in heart preparations partially depolarized by potassium, was investigated in guinea‐pig ventricular muscle in order to elucidate the mechanism of the positive inotropic effect mediated via α‐adrenoceptors.

In preparations in which fast sodium channels were inactivated by K+‐rich medium (22 mm) slow electrical responses as well as contractions were consistently induced by high concentrations of phenylephrine (10−4 to 3 × 10−4 m) and synephrine (3 × 10−4 m).

The restorative effects of both phenylephrine and synephrine were unaffected by phentolamine (10−5 m) but were readily abolished by practolol (10−5 m) or sotalol (10−5 m).

Methoxamine induced a dose‐dependent positive inotropic effect in ventricular strips paced at 0.5 Hz in normal Tyrode solution; the maximum increase in contractile tension was obtained with methoxamine 10−4 m. However, at the same concentration, the amine did not induce slow electrical responses in potassium‐depolarized preparations.

It is concluded that the induction of slow responses by phenylephrine and synephrine is due to β‐adrenoceptor stimulation, and that the increase in cardiac contractility caused by α‐adrenoceptor stimulation does not involve an increase in slow inward calcium current.
FACILITATION OF SYMPATHETIC NEUROTRANSMISSION IN THE RAT ANOCOCCYGEUS MUSCLE BY PROSTAGLANDINS D2 AND F2α
Authors: BEDWANI J.R. , HILL SIAN E.
Published: July 2012

Investigations were made into the effects of prostaglandins D2 (PGD2) and F2α (PGF2α) on the responses of the rat anococcygeus muscle to field stimulation of intrinsic motor (sympathetic) and inhibitory nerves, and to exogenous noradrenaline.

PGD2 (2.8 × 10−6 mol/1) substantially increased the motor responses to field stimulation at all frequencies tested (2 to 32 Hz), and caused a smaller increase in the responses to noradrenaline.

PGF2α (2.8 × 10−6 mol/1) strongly potentiated the motor responses to field stimulation (2 to 32 Hz) and also to noradrenaline. This prostaglandin had quantitatively similar effects on the responses to both types of stimulus.

PGD2 was without effect on the inhibitory responses evoked by field stimulation in the presence of guanethidine. PGF2α seemed to reduce the inhibitory responses to low frequencies of stimulation (0.5 to 1.5 Hz), but this effect was marginal.

The results suggest that PGD2 facilitates sympathetic neurotransmission in this tissue by both pre‐ and post‐junctional actions. The effect of PGF2α seems likely to be mediated predominantly post‐junctionally.
INHIBITION OF REFLEX VAGAL BRADYCARDIA BY A CENTRAL ACTION OF 5‐HYDROXYTRYPTOPHAN
Authors: TADEPALLI A.S.
Published: July 2012

Vagally mediated reflex bradycardia was elicited in spinal cats with intravenous pressor doses of noradrenaline. Administration of 5‐hydroxytryptophan (1.5 and 3 mg total dose) into the fourth cerebral ventricle reduced the reflex bracycardia.

Inhibition of central amino acid decarboxylase with R044602 prevented the effects of 5‐hydroxytryptophan. After intravenous administration of 5‐hydroxytryptophan, vagal reflex bradycardia was not affected.

Results suggest that 5‐hydroxytryptophan acts in the CNS to inhibit baroreceptor‐mediated vagal reflex bradycardia and that action is mediated via conversion to 5‐hydroxytryptamine.
FURTHER OBSERVATIONS ON THE UTILIZATION OF ADENOSINE TRIPHOSPHATE IN RAT MAST CELLS DURING HISTAMINE RELEASE INDUCED BY THE IONOPHORE A23187
Authors: JOHANSEN TORBEN
Published: July 2012

The relation between A23187‐induced histamine release and the energy metabolism of the rat mast cells has been studied.

Ethacrynic acid was used as an inhibitor of calcium‐induced histamine release from mast cells primed with the ionophore A23187, and to study calcium‐induced changes in the adenosine triphosphate (ATP) content and the rate of lactate production of A23187‐primed mast cells.

Ethacrynic acid by itself decreased the rate of glycolytic ATP production.

By measurement of the ATP content and the lactate production of mast cells with or without secretory activity, the increased demand of energy for exocytosis was estimated to be equivalent to 0.14 pmol of ATP per 103 mast cells.
THE EFFECT OF LUMBAR SYMPATHETIC STIMULATION ON THE VASCULATURE OF BONE
Authors: TRAN MARIE‐ANTOINETTE
Published: July 2012

The nutrient artery to the tibia of anaesthetized dogs was perfused at a constant rate by blood from the femoral artery and the perfusion pressure in the artery, the intramedullary pressure of the bone and the pressure in the nutrient vein recorded.

Low frequency stimulation (1 to 5 Hz) of the lumbar sympathetic chain always increased the perfusion pressure but the intramedullary pressure sometimes increased, sometimes decreased and sometimes remained unchanged.

The α‐adrenoceptor blocking agents, phentolamine (1 mg/kg i.v.) and dihydroergotamine (0.5 mg/kg i.v.) reduced or abolished these effects whereas the β‐adrenoceptor blocking agent, propranolol (1 mg/kg i.v.) did not modify them.

The nutrient vein end pressure did not differ significantly from the intramedullary pressure and underwent similar variations during stimulation of the lumbar sympathetic chain.
THE EFFECT OF PROSTAGLANDIN E2 MICROINJECTED INTO THE RAT HYPOTHALAMUS ON URINARY EXCRETION OF WATER AND SODIUM
Authors: FUJIMOTO SEIGO
Published: July 2012

Effects of prostaglandin E2 (PGE2) microinjected into the supraoptic (SON) and the ventromedial nuclei of the hypothalamus (VMH) on urine outflow were studied in rats anaesthetized with ethanol.

PGE2 injected into the SON caused antidiuresis and increased the excretion rate of Na+. These effects of PGE2 were prevented by pretreatment with phentolamine but not propranolol, suggesting that they are mediated by α‐adrenoceptors in the SON.

PGE2 injected into the VMH caused diuresis and increased the excretion rate of Na+. These effects were prevented by pretreatment with propranolol but not phentolamine, suggesting that they are mediated through β‐adrenoceptors in the VMH.
4‐AMINOPYRIDINE BLOCKADE OF NEURONAL DEPRESSANT RESPONSES TO ADENOSINE TRIPHOSPHATE
Authors: PERKINS M.N. , STONE T.W.
Published: July 2012

Adenosine, adenosine monophosphate and adenosine triphosphate (ATP) depressed the firing rate of neurones in the rat cerebral cortex when applied by microinontophoresis.

4‐Aminopyridine, also applied iontophoretically, blocked the depressant effects of the purines, without affecting responses to γ‐aminobutyric acid (GABA). This blockade was effected against purine depressions of both spontaneous and glutamate‐evoked activity, suggesting that the interaction occurred postsynaptically.
ACTIONS OF LOCALLY ADMINISTERED ADRENOCEPTOR AGONISTS ON INCREASED PLASMA PROTEIN EXTRAVASATION AND BLOOD FLOW IN GUINEA‐PIG SKIN
Authors: BEETS J.L. , PAUL W.
Published: July 2012

Bradykinin‐induced increased plasma protein extravasation (IPPE) and blood flow have been assessed in guinea‐pig skin by isotopic methods.

The effects of a range of adrenoceptor agonists on these parameters have been investigated.

α‐Adrenoceptor agonists inhibited IPPE and reduced cutaneous blood flow. The potency of α‐agonists as inhibitors of IPPE correlated with their vasoconstrictor effects. The actions of noradrenaline on both IPPE and blood flow were blocked by phentolamine but not by propranolol.

β‐Adrenoceptor agonists inhibited IPPE at doses which either increased or caused little change in cutaneous blood flow. Isoprenaline inhibition of IPPE was reduced by propranolol but was unaffected by phentolamine.

The inhibitory action of α‐agonists on IPPE can be explained by a reduction in blood flow to the affected site. Beta agonist inhibition is not due to effects on blood flow but is probably caused by a reduction in permeability of the microvessels.
REGULATION OF NORADRENALINE OVERFLOW IN RAT CEREBRAL CORTEX BY PROSTAGLANDIN E2
Authors: HILLIER KEITH , TEMPLETON WILMA W.
Published: July 2012

The effects of prostaglandin E2 (PGE2), PGF2α and PGI2 and of inhibitors of prostaglandin synthesis and action, on the K+‐evoked [3H]‐noradrenaline ([3H]‐NA) overflow from rat cerebral cortex slices have been investigated.

PGE2 reduced, while indomethacin (a prostaglandin synthesis inhibitor) or SC 19220 (a prostaglandin receptor antagonist) increased, the evoked overflow compared with controls.

The inhibition of [3H]‐NA overflow by PGE2 was dose‐dependently antagonized by SC 19220.

The results indicate that PGE2 modulates NA release in rat cerebral cortex in vitro.