bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uptake, disposition and metabolism of histamine in isolated heart preparations
Authors: MANNAIONI P. F. , MORONI F. 
Published: July 2012

Summary
The uptake and metabolism of histamine by the guinea‐pig heart and by the isolated electrically driven guinea‐pig left atria was studied with both labelled and unlabelled histamine.
Histamine uptake took place against a concentration gradient and, at low concentrations, this was blocked by hypoxia plus glucose deprivation or by a toxic dose of ouabain.
The histamine taken up was retained by cardiac tissues and mainly metabolized into methyl‐histamine and other metabolites. The uptake and metabolism of histamine was higher in atria than in ventricles thus reflecting the regional distribution of endogenous histamine and mast cell numbers.
The uptake and metabolism of histamine were greatly reduced in hearts which had been depleted of mast cells, by combining cardiac anaphylaxis and (+)‐tubocurarine (1 mg/ml), but pretreatment of guinea‐pigs with 6‐hydroxydopamine failed to affect uptake of total radioactivity in the isolated left atria.
In the guinea‐pig heart histamine appears to be taken up, stored and metabolized in at least two pools, one of which is linked to the mast cells.
The number of muscarinic receptors in chick amnion muscle
Authors: CUTHBERT A. W. , YOUNG J. M. 
Published: July 2012

Summary
[3H]‐Propyl benzilylcholine mustard ([3H]‐PrBCM) an irreversible specific antagonist of muscarinic acetylcholine receptors, has been used to label the muscarinic receptors in the aneuronal muscle of isolated 11 day amniotic membranes of chick embryos.
This muscle was found to have about 9 fmol/mg dry weight of receptor material. This is only 1–2% of the amount found in intestinal muscle.
Pharmacological studies with isolated amniotic membranes using PrBCM show that labelling is to functional receptors and that the receptor reserve is small.
The significance of the difference in receptor reserve in innervated and aneuronal plain muscle is discussed.
The β‐adrenoceptor blocking properties of the α‐methyl analogues of propranolol and practolol in the anaesthetized dog
Authors: LEVY B. 
Published: July 2012

Summary
The β‐adrenoceptor blocking properties of α‐methyl propranolol and α‐methyl practolol were determined in anaesthetized dogs according to their abilities to modify the isoprenaline‐induced effects on diastolic pressure, heart rate, myocardial contractile force, femoral arterial blood flow and pulmonary airway resistance.
α‐Methyl propranolol shifted the isoprenaline dose‐response curves for the fall in diastolic pressure and the positive inotropic and chronotropic responses to the right in a parallel manner yielding pA2 and slope values of 6·66 (0·92), 6·34 (0·77) and 6·59 (0·61) respectively. The slopes of the graphs for determining pA2 values for the cardiac β‐adrenoceptor blocking properties of α‐methyl propranolol were significantly less than 1 and indicated a mechanism other than simple, competitive, reversible antagonism.
α‐Methyl propranolol exerted a much weaker blockade of respiratory smooth muscle β‐adrenoceptors than has been reported for propranolol.
α‐Methyl practolol exerted a weaker blocking effect on myocardial β‐adrenoceptors than has been reported for practolol. No significant blockade of vascular or respiratory smooth muscle β‐adrenoceptors occurred after a total cumulative dose of 10 μg/kg of α‐methyl practolol.
α‐Methyl substitution of propranolol and practolol reduces the potency but increases the selectivity of their β‐adrenoceptor blocking properties.
The β‐adrenoceptors subserving cardiac stimulation, vasodilatation and bronchodilatation are representative of three different β‐adrenoceptor sub‐types in the dog.
ATROPINE‐RESISTANT EFFECTS OF THE MUSCARINIC AGONISTS McN‐A‐343 AND AHR 602 ON CARDIAC PERFORMANCE AND THE RELEASE OF NORADRENALINE FROM SYMPATHETIC NERVES OF THE PERFUSED RABBIT HEART
Authors: FOZARD J.R. , MUSCHOLL E. 
Published: July 2012

The effects of 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammonium chloride (McN‐A‐343) and N‐benzyl‐3‐pyrrolidyl acetate methobromide (AHR 602) on cardiac performance and noradrenaline release from terminal sympathetic fibres were measured in isolated perfused hearts of rabbits.
In the presence of sufficient atropine to block muscarinic receptors, high concentrations of McN‐A‐343 and AHR 602 caused no cardiac stimulation and there was no increase in the resting output of noradrenaline into the perfusates.
McN‐A‐343 and AHR 602 increased both the mechanical responses and the transmitter overflow evoked by electrical stimulation of the sympathetic nerves (SNS) but inhibited both parameters during perfusion with 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP). The effects were atropine‐resistant and qualitatively similar to those seen with cocaine. Hexamethonium inhibited DMPP, but affected neither SNS per se nor the facilitatory effects of McN‐A‐343 and AHR 602 on SNS.
McN‐A‐343, cocaine and desipramine (but not AHR 602 or hexamethonium) blocked the net cardiac noradrenaline uptake and increased the positive chronotropic effect of noradrenaline.
Prior perfusion with concentrations of cocaine and desipramine sufficient to block uptake reduced or abolished the facilitatory effects of both McN‐A‐343 and AHR 602 on SNS.
Cocaine, McN‐A‐343 and AHR 602 displayed local anaesthetic properties on the guinea‐pig wheal and frog nerve plexus tests, and their relative potencies in this respect were similar to those for inhibition of DMPP‐evoked transmitter overflow. Hexamethonium did not produce local anaesthesia.
The results indicate that the facilitated release of noradrenaline after SNS and the inhibition of release after DMPP produced by McN‐A‐343 and AHR 602 are the result of their combined local anaesthetic action and inhibition of amine uptake.
DISSOCIATION OF 5‐HYDROXYTRYPTAMINE EFFECTS ON MYOCARDIAL CONTRACTILITY AND CYCLIC AMP ACCUMULATION
Authors: BENFEY B.G. , COHEN J. , KUNOS G. , VERMES‐KUNOS I. 
Published: July 2012

5‐Hydroxytryptamine increased the contractility of the isolated rat atrium and produced a small rise in cyclic 3′,5′‐adenosine monophosphate (cyclic AMP) accumulation in rat heart slices. These effects were similar to those of tyramine.
Incubation with phenoxybenzamine prevented the inotropic effect of 5‐hydroxytryptamine but did not inhibit the rise in cyclic AMP accumulation.
A single injection of reserpine 24 h before the experiment did not inhibit the inotropic effect of 5‐hydroxytryptamine but prevented the rise in cyclic AMP accumulation.
It is concluded that in the rat 5‐hydroxytryptamine increases cardiac contractility chiefly by a direct effect which is blocked by phenoxybenzamine, whereas it increases myocardial cyclic AMP accumulation indirectly by releasing endogenous catecholamines. Cardiac contractility may thus be increased without a rise in cyclic AMP accumulation, and cyclic AMP accumulation may be increased without a rise in contractility.
THE MODIFICATION OF LUMBAR MOTONEURONE EXCITABILITY BY STIMULATION OF A PUTATIVE 5‐HYDROXYTRYPTAMINE PATHWAY
Authors: BARASI S. , ROBERTS M.H.T. 
Published: July 2012

Changes in lumbar motoneurone excitability were monitored by recording spinal reflex activity from the ventral roots of rats anaesthetized with fluothane.
Electrical stimulation of nucleus raphes medianus increased the amplitude of the monosynaptic reflex via a pathway having a slow conduction velocity. Stimulation elsewhere in the lower brain stem was less effective. This increase in motoneurone excitability was potentiated by the intravenous injection of l‐tryptophan and reduced by intravenous injections of lysergic acid diethylamide (LSD), methysergide or Cinanserin.
Extracellular field potential responses to stimulation of dorsal or ventral roots were recorded with six barrelled microiontophoresis electrodes. Stimulation of nucleus raphes medianus and iontophoretic application of 5‐hydroxytryptamine (5‐HT) both increased the excitability of lumbar motoneurones as reflected by an increase in field potential amplitude.
Responses to both stimulation of raphe nuclei and iontophoretic application of 5‐HT were reduced by iontophoretic application of Cinanserin and methysergide.
The similarities of the responses of lumbar motoneurones to applied 5‐HT and activity within the raphe‐spinal pathway are discussed. It is suggested that activity within the raphe‐spinal pathway can increase lumbar motoneurone excitability via the release of 5‐HT in the ventral horn of the spinal cord.
BIOLOGICAL ACTIONS In vivo AND In vitro OF TWO γ‐AMINOBUTYRIC ACID (GABA) ANALOGUES: β‐CHLORO GABA AND β‐PHENYL GABA
Authors: BUU N.T. , VAN GELDER N.M. 
Published: July 2012

The synthesis of two analogues of γ‐aminobutyric acid (GABA), β‐chloro GABA and β‐phenyl GABA is described.
The activity of brain GABA aminotransferase was inhibited by β‐chloro GABA (5.7 × 10−5 M) and β‐phenyl GABA (4.6 × 10−3 M) in a competitive manner with GABA.
β‐Chloro GABA exhibited 50% of the inhibitory activity of GABA in blocking the discharge of the crayfish stretch receptor neurone; β‐phenyl GABA had no detectable effect.
Injection of β‐phenyl GABA (200 mg/kg) into normal or epileptic cats (cobalt) caused the appearance of synchronized slow‐wave EEG activity.
Administration of β‐chloro GABA (200 mg/kg) to epileptic cats (cobalt) produced a temporary diminution or abolition of epileptic discharges while causing no alteration in normal EEG activity.
β‐Chloro GABA and β‐phenyl GABA had no effect on the concentrations of catecholamines or of amino acids in mouse brain.
The results suggest that both β‐chloro GABA and β‐phenyl GABA may pass the blood‐brain barrier.
A STUDY OF THE METABOLIC REQUIREMENTS FOR THE CONTRACTILE ACTION OF ANGIOTENSIN UPON GUINEA‐PIG ILEUM
Authors: CROCKER ANN D. , WILSON K.A. 
Published: July 2012

Acetylcholine and angiotensin elicit a contraction of guinea‐pig ileum. The metabolic requirements for these actions have been investigated.
The angiotensin‐induced response was far more dependent upon the presence of glucose than was the response to acetylcholine.
Anoxia and oxidative enzyme inhibition preferentially reduced the angiotensin‐induced response.
The significance of these results is discussed. It is concluded that the response to angiotensin is dependent upon an ATP source distinct from that required by the contractile process. It is further shown that this energy‐dependent stage cannot be identified with the indirect, cholinergic component of the angiotensin response in this tissue.
CARDIOVASCULAR ACTIONS OF PROSTAGLANDIN C IN THE CAT AND DOG
Authors: JONES R.L. , KANE KATHLEEN A. , UNGAR A. 
Published: July 2012

Prostaglandin C2 causes a prolonged fall in arterial blood pressure in the cat.
At constant heart rate this fall in arterial pressure is accompanied by falls in stroke volume, left ventricular end diastolic pressure, and left ventricular dP/dt max.
If mean aortic pressure and left ventricular end diastolic pressure are held constant as well as heart rate, prostaglandins C2 and E2 do not affect dP/dt max in the cat.
In the dog, under similarly controlled conditions, prostaglandins C2 and E2 raise dP/dt max.
We conclude that prostaglandins E2 and C2 have no direct inotropic action in the cat, but both have a direct positive inotropic action in the dog.
EFFECTS OF TIPRENOLOL, PRACTOLOL AND PROPRANOLOL ON EXPERIMENTAL VENTRICULAR TACHYARRHYTHMIAS
Authors: ALLEN J.D. , SHANKS R.G. 
Published: July 2012

Low doses of tiprenolol (0.01–0.02 mg/kg) and propranolol (0.05 mg/kg) abolished the ventricular arrhythmias produced by the intravenous injection of adrenaline in anaesthetized dogs respired with halo thane.
Larger doses of tiprenolol (2.0–4.0 mg/kg) restored sinus rhythm in four of five dogs with ventricular tachycardia produced by toxic doses of ouabain. Propranolol (2.0–4.0 mg/kg) had the same effect in each of four dogs.
Both tiprenolol (4.0–8.0 mg/kg) and propranolol (4.0 mg/kg) increased the frequency of sinus beats and reduced the ventricular rate in dogs with ventricular tachycardia 20–44 h after ligation of a coronary artery.
Practolol (0.5–16.0 mg/kg) did not reduce the ventricular rate or increase the frequency of sinus beats in dogs with ventricular tachycardia after ligation of a coronary artery.
In dogs with ouabain‐induced ventricular tachycardia mean arterial pressure was reduced after the administration of tiprenolol (0.5–8.0 mg/kg) or propranolol (4.0–8.0 mg/kg). Depression of sinus and atrioventricular nodal function, and of intraventricular conduction developed in some of the dogs given tiprenolol (4–8 mg/kg) or propranolol (8.0 mg/kg).
The administration of tiprenolol (1.0–8.0 mg/kg) or propranolol (4.0–8.0 mg/kg) depressed the arterial pressure and caused the deaths of some dogs in which a coronary artery had been ligated. Such deaths did not occur in the group which had been given toxic doses of ouabain.
THE PROPERTIES OF MUSCARINIC RECEPTORS IN MAMMALIAN CEREBRAL CORTEX
Authors: BURGEN A.S.V. , HILEY C.R. , YOUNG J.M. 
Published: July 2012

The reaction of tritiated propylbenzilylcholine mustard ([3H]‐PrBCM; N‐2′‐chloroethyl‐N‐[2″,3″‐3H2]‐propyl‐2‐aminoethylbenzilate) with homogenates of mammalian brain has been studied.
The uptake can be divided into an atropine‐sensitive component of fixed capacity (380 pmol/g protein in the rat) and an atropine‐insensitive part.
The atropine‐sensitive portion is identified as muscarinic receptor by its insensitivity to nicotinic antagonists and anticholinesterases and its sensitivity to a range of muscarinic antagonists.
The uptake of [3H]‐PrBCM is also inhibited by muscarinic agonists and there is reasonable quantitative agreement between the affinities of agonists estimated in this way and in intact tissues by physiological responses.
The fraction of [3H]‐PrBCM uptake inhibited by muscarinic antagonists and agonists is the same.
The amount of receptor found in six mammalian species was inversely related to the size of the brain, but the rates of alkylation and the sensitivity to atropine were not dissimilar.
STRAIN DIFFERENCES IN THE INHIBITION BY HEMICHOLINIUM‐3 OF THE PRESSOR RESPONSE TO INTRAVENTRICULAR INJECTION OF NEOSTIGMINE IN RATS
Authors: BREZENOFF H.E. , RUSIN JUDITH 
Published: July 2012

The pressor response to intracerebroventricular (i.c.v.) injections of neostigmine was examined in three groups of Sprague‐Dawley rats (MFS, CS and CFE) obtained from different breeders and in Long‐Evans rats (MLE) obtained from one of the same breeders. All rats responded with a rise in blood pressure to i.c.v. injection of neostigmine, although the CFE strain was 6‐fold less sensitive to the drug than were the other strains.Prior i.c.v. injection of hemicholinium‐3 (HC‐3; 0.4 μg) reduced by more than 50% the pressor response in the two strains obtained from the same breeder (MFS and MLE) and caused an 11% reduction in the CS strain. In contrast, the pressor response in CFE rats was not affected by as much as 40 μg of HC‐3, although this dose decreased the response to neostigmine by 47–66% in the other three strains.
THE CARDIOVASCULAR EFFECTS OF l‐DOPA IN THE PITHED RAT
Authors: EDEN E. , NASMYTH P.A. 
Published: July 2012

l‐DOPA (1–2 mg i.v.) in the pithed rat reduced the arterial and increased the venous pressure responses to noradrenaline.
Infusions of dopamine (4–8 μg kg−1 min−1) and noradrenaline (500 ng kg−1 min−1) also reduced the pressor responses to noradrenaline. The pressor response did not recover after stopping dopamine infusions, but it usually did so after stopping noradrenaline infusions.
The effect of l‐DOPA on the response to noradrenaline was prevented by the prior injection of the dopa decarboxylase inhibitor NSD 1024.
The prior injection of the dopamine‐β‐hydroxylase inhibitor diethyldithiocarbamate, only partially prevented the effect of l‐DOPA on pressor responses to noradrenaline.
The perfusion of noradrenaline (400 ng kg−1 min−1) together with Krebs solution (10 ml/min) through an organ bath containing an isolated aortic strip, depressed the response of the strip to doses of noradrenaline after the infusion was stopped. Infusions of dopamine (0.5–8.0 μg kg−1 min−1) had a similar effect. Fifteen minutes after adding l‐DOPA (0.5 mg) to the bath and 10 min after washing it out, the response to noradrenaline was depressed in three out of four experiments.
Infusions of noradrenaline (1 μg kg−1 min−1) in an isolated heart perfused by Langendorf's method blocked the response to injected noradrenaline whilst perfusion was in progress. Infusions of dopamine (4–8 μg kg−1 min−1) or of l‐DOPA (200 μg kg−1 min−1) did not have this effect.
It is concluded that the effect of l‐DOPA on pressor responses to noradrenaline in the pithed rat are mediated by its conversion to dopamine and noradrenaline.
THE SPECIFICITY OF SOME AGONISTS AND ANTAGONISTS FOR NICOTINE‐SENSITIVE RECEPTORS IN GANGLIA
Authors: BARLOW R.B. , BOWMAN FRANCES , ISON R.R. , McQUEEN D.S. 
Published: July 2012

The guinea‐pig isolated ileum has been used to estimate the ability of substituted phenylalkylonium salts (related to nicotine) to stimulate or block receptors in ganglia. The effects of hexamethonium were used to indicate which were the most specific ganglion stimulants; these were tested on the blood‐pressure of pithed rats and for neuromuscular blocking activity on the rat diaphragm preparation.
m‐Hydroxyphenylpropyltrimethylammonium and 3,4‐dihydroxyphenethyltrimethyl‐ammonium (coryneine, ‘quaternary dopamine’) were the most active and specific ganglion stimulants but their usefulness in vivo may be limited by their neuromuscular blocking activity. The analogous tertiary compounds are being investigated.
The affinities of substances which were blocking agents at ganglionic receptors were measured on the isolated ileum with m‐hydroxyphenylpropyltrimethylammonium as agonist. The affinities of selected compounds for postganglionic receptors were measured in experiments on the ileum in the presence of hexamethonium and with carbachol as agonist. Some of the compounds were tested for neuromuscular blocking activity on the rat diaphragm.
Phenylbutyldiethylamine had ganglion‐blocking activity greater than pempidine and little postganglionic blocking or neuromuscular blocking activity. Its triethylammonium analogue had higher ganglion‐blocking activity but had appreciable neuromuscular blocking activity.
The aromatic ring system is not essential either for activity or affinity and the effects of substituents are not related to their effects on electron distribution. Stimulant activity is enhanced only by hydroxyl or amino groups in suitable positions; it is not improved by the presence of rigid features (double or triple bonds or a cyclopropane ring) in the side chain. Affinity is slightly increased by chloro or bromo groups in suitable positions but the unsubstituted compounds are among those with the highest affinity. Substituents have similar effects on affinity for postganglionic receptors, though for these receptors the compounds mostly have only about one‐tenth of their affinity for ganglionic receptors.
BICUCULLINE AND THE FROG SPINAL CORD
Authors: PIXNER D.B. 
Published: July 2012

The effects of bicuculline on dorsal and ventral root activity and upon the depressant effect of γ‐aminobutyric acid (GABA) and glycine on ventral root responses have been studied on the isolated spinal cord of the frog.
In the absence of stimulation, the alkaloid induced a variety of activity of which the most notable was phasic simultaneous slow wave depolarization in the dorsal and ventral roots which could be reduced or suppressed by magnesium.
With low concentrations of bicuculline, the adjacent dorsal root response evoked by a single stimulus was depressed maximally before an increase in the ventral root response could be discerned.
The bicuculline‐induced dorsal root activity (in the absence of stimulation) was still apparent at times when the evoked dorsal root response was reduced.
Bicuculline did not differentiate between the depressant effects of GABA and glycine on the evoked ventral root responses.
The excitant effects of bicuculline reported here did not appear to be attributable to specific antagonism of the postsynaptic depressant action of GABA.
MECHANISM OF CATECHOLAMINE ANTAGONISM IN RAT HEART PRODUCED BY PILOCARPINE AND RELATED DRUGS
Authors: SADAVONGVIVAD C. , SANVARINDA P. , SATAYAVIVAD JUTAMAAD 
Published: July 2012

High concentrations of pilocarpine and methacholine consistently lowered the potencies of a series of adrenoceptor agonists as shown by displacement of complete cumulative dose‐effect curves for their positive chronotropic action on rat isolated atria. The order of potency of the agonists was characteristic of β‐adrenoceptor activation and this was converted to the type which characterizes α‐adrenoceptor activation when pilocarpine was present.
Propranolol effectively blocked the adrenoceptor agonists in the presence of pilocarpine and phentolamine abolished the antagonistic actions of pilocarpine. Atropine, which by itself did not affect the action of the adrenoceptor agonists, abolished both the bradycardia and antagonism produced by pilocarpine.
It is concluded that pilocarpine antagonizes adrenoceptor agonists by muscarinic cholinoceptor activation without involving classical adrenoceptors.
PHARMACOLOGICAL OBSERVATIONS ON THE HYPOTENSIVE ACTION OF EXTRACTS OF TELEOST FISH UROPHYSES (UROTENSIN I) IN THE RAT
Authors: LEDERIS K. , MEDAKOVIĆ M. 
Published: July 2012

Intravenous injections of urotensin I regularly caused a long‐lasting, dose‐related, lowering of blood pressure and an increase in heart rate in conscious rats, or a reduction in perfusion pressure in the isolated hind limb of the rat.
After subcutaneous administration, the hypotensive effect of urotensin I was greater in extent and in duration (> 24 hours).
Anaesthesia with ether, chloralose, pentobarbitone and thiobarbitone caused a decrease in blood pressure and only slightly diminished the hypotensive effect of urotensin.
Mecamylamine, hexamethonium, atropine, phenoxybenzamine, propranolol and diphenhydramine did not alter the effect of urotensin in conscious rats or in the isolated hind limb, although the effects of the respective agonists, i.e. nicotine, acetylcholine, noradrenaline, isoprenaline and histamine were inhibited.
In conscious rats, pressor effects of adrenaline, noradrenaline, nicotine and angiotensin II, and depressor effects of acetylcholine and bradykinin, were decreased or inhibited, whereas the hypotensive effect of phenoxybenzamine was potentiated by previous administration of urotensin I. Carotid occlusion reflex was partially inhibited by lower doses of urotensin and abolished by higher doses in rats lightly anaesthetized with chloralose. Urotensin elicited postural hypotension in rats anaesthetized with pentobarbitone.
The increase in heart rate produced by urotensin was not affected by phenoxybenzamine, but was abolished by propranolol or ganglion blocking agents (mecamylamine or hexamethonium).
It is concluded that urotensin elicits hypotension in the rat by a direct dilatory action on the resistance vessels causing a simultaneous reflex tachycardia.
THE EFFECT OF PHASE‐SHIFT ON THE PASSIVE AVOIDANCE RESPONSE IN RATS AND THE MODIFYING ACTION OF CHLORDIAZEPOXIDE
Authors: DAVIES J.A. , NAVARATNAM V. , REDFERN P.H. 
Published: July 2012

In rats trained to a 12 h light‐12 h dark cycle, advancing the phase by 6 h produced a resynchronization of the 24 h variation in passive avoidance response (PAR) which was completed after 10 days.
The attainment of the new steady state was preceded by a period of disruption which was greatest 5 days after phase‐shift.
The presence of chlordiazepoxide (62.5–500 μg/ml) in the drinking water during the days after phase‐shift produced a dose‐dependent lessening of the disruptive effect of phase‐shift, and a more rapid adaptation to the new light‐dark cycle.