bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of age, species and adrenaline on the recovery of isolated atria from anoxia
Authors: PENN R. G. 
Published: July 2012

Summary
The rate of recovery of the force of contraction of isolated atria from different species of mature animals after 1 hour of anoxia was recorded.
Atria from rabbits of different ages were also exposed to anoxia. Atria from rabbits, ranging in age from 8 days to 3 years, were essentially similar in their recovery from anoxia, which was significantly slower than that of atria taken from rabbit foetuses at the 25th day of gestation.
Atria from human foetuses at 12–16 weeks of gestation recovered from anoxia much faster and more completely than any other atria studied and it is postulated that this may be due, in part, to the concentration of endogenous catecholamines being low.
The addition of propranolol to the organ bath had no effect on the recovery of atria from anoxia but prevented the action of added adrenaline, which manifests itself in a slowing of the rate and incompleteness of the recovery.
The contribution of the sympathetic nervous system to the development and maintenance of experimental hypertension in the rat
Authors: FINCH L. , LEACH G. D. H. 
Published: July 2012

Summary
Experimental hypertension in the rat, induced either by renal artery stenosis or by treatment with deoxycorticosterone acetate (DCA) developed maximally over a period of 8 weeks. In both types of hypertension the rate of development was unaffected by immunosympathectomy or by chemical sympathectomy following the administration of 6‐hydroxydopamine.
The effect of 6‐hydroxydopamine on chronic renal hypertensive rats was to produce a hypotensive action of longer duration than when similarly administered to DCA‐induced hypertensive or normotensive rats. Reserpine (5–10 mg/kg intraperitoneally) produced a more marked hypotensive effect on both types of hypertensive rats although it was of much shorter duration.
It is concluded that experimental hypertension of renal origin or induced by DCA treatment can develop even though most of the sympathetic nervous system has been destroyed. The maintenance of chronic hypertension in these conditions may depend on the adrenal glands or a hormonal system as yet undetected.
The release of acetylcholine by acetylcholine in the cat's superior cervical ganglion
Authors: COLLIER B. , KATZ H. S. 
Published: July 2012

Summary
The experiments described in this paper tested the effect of acetylcholine (ACh), carbachol or preganglionic nerve stimulation on the release of ACh from the cat's perfused superior cervical ganglion; radioactive tracer methods were used.
When the ganglion's transmitter store of ACh had been labelled, radioactive ACh was released by nerve stimulation (5 Hz for 2 min), but there was no release by ACh (0.15–15 μg) or by carbachol (1–10 μg) when these drugs were injected close to the ganglion. Perfusion with low or moderate concentrations of ACh (015–5 μg/ml) also failed to release ACh, but high concentrations (15–50 μg/ml) released a small amount of labelled material. There was no correlation between ganglion stimulation by ACh and release of radioactivity.
Ganglion‐blocking concentrations of ACh did not reduce the release of ACh during continuous nerve stimulation.
When resting (unstimulated) ganglia were perfused with 3H‐choline and eserine, the extra ACh synthesized and stored by such ganglia (surplus ACh) was labelled. Preganglionic nerve stimulation (5 Hz for 2 min) did not release surplus ACh, but perfusion with ACh (0.5–15 μg/ml), or injection of carbachol (0.5–2.5 μg) did.
Surplus ACh released by ACh or by carbachol did not contribute to the ganglion stimulating effect of either drug.
It is concluded that the presynaptic effects of ACh are not of physiological importance.
β‐Adrenoceptor stimulating properties of para‐dimethylaminobenzaldehyde
Authors: GHOURI M. S. K. , SHIBATA S. 
Published: July 2012

Summary
Studies on the various isolated tissues indicate that para‐dimethylaminobenzaldehyde (DMAB) is a β‐adrenoceptor stimulant. DMAB is antagonized by the β‐adrenoceptor blocking agent, MJ 1999, but not by the α‐adrenoceptor blocking agent, phentolamine.
A study of dose‐response relationships suggests a competitive interaction between MJ 1999 and DMAB.
DMAB was about 122 times less potent than isoprenaline on the isolated guinea‐pig tracheal preparation. The effects of DMAB on isolated rabbit atria were not only very weak, but were also very brief. On this tissue, DMAB was respectively 72,000 and 55,400 times less active than isoprenaline in producing positive chronotropic and inotropic effects. DMAB caused the relaxation of the guinea‐pig taenia coli and the rabbit ileum. These actions were very weak in comparison with those of isoprenaline.
These results suggest that a compound (DMAB) structurally different from isoprenaline may mimic isoprenaline responses by stimulating β‐adrenoceptors through different mechanisms.
Long‐lasting convulsant effect on the cerebral cortex of Naja naja venom
Authors: BHARGAVA V. K. , HORTON R. W. , MELDRUM B. S. 
Published: July 2012

Summary
A neurotoxic fraction has been prepared from Indian cobra venom (Naja naja) by column chromatography on CM Sephadex.
When assayed for lethality in mice, or for neuromuscular blocking potency in the rat phrenic nerve‐diaphragm preparation, this fraction was 2.4–2.9 times as potent as whole venom.
Application of either whole venom (0.5–1.0 mg/ml) or the neurotoxic fraction (0.25–1.0 mg/ml) to the exposed cerebral cortex of the rat led to the appearance in the somatosensory evoked potential of abnormal negative waves, resembling in amplitude and latency those produced by the cortical application of strychnine or curare.
This effect differed from that produced by strychnine or curare in that after washing off the toxin the abnormal responses persisted for as long as the experiment continued (8–9 hours).
Effects of lignocaine and propranolol on experimental cardiac arrhythmias
Authors: ALLEN J. D. , SHANKS R. G. , ZAIDI S. A. 
Published: July 2012

Summary
The effects of intravenous injection of lignocaine and propranolol were studied in dogs.
Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished in four out of six dogs by lignocaine. Propranolol was effective in all three dogs tested.
Intravenous infusion of lignocaine at (0·2 and 1·0 mg/kg)/min to total doses of 3·0 ± 1·0 and 2·2 ± 0·5 mg/kg, respectively, abolished the ventricular tachycardia produced in anaesthetized dogs by ouabain. A similar effect was produced by infusion of propranolol at (0·2 mg/kg)/min to a total dose of 1·9 ± 0·4 mg/kg. Intravenous injection of single doses of lignocaine (4·0–8·0 mg/kg) also abolished the arrhythmia.
The frequency of the ventricular ectopic beats occurring in conscious dogs 20–44 h after ligation of the anterior descending branch of the left coronary artery was reduced, with an increase in the number of sinus beats, after intravenous injection of lignocaine (8·0 mg/kg). Larger doses produced excitement. Propranolol (4·0 mg/kg) had a greater effect than the same dose of lignocaine but after 8·0 mg/kg, three of the four dogs died.
Propranolol was more effective than lignocaine in abolishing the three different types of arrhythmia.
Dose‐response curves showed that lignocaine was more active in abolishing the ouabain induced arrhythmia than the halothane‐adrenaline arrhythmia and was least active on the arrhythmia caused by ligation of the coronary artery.
Differentiation between the actions of acetylcholine and tetramethylammonium on the isolated taenia of the guinea‐pig caecum by hemicholinium‐3
Authors: MITCHELSON F. 
Published: July 2012

Summary
Contractions of the isolated taenia of the guinea‐pig caecum produced by acetylcholine and TMA were examined in the presence of various antagonists and anticholinesterases.
Hemicholinium‐3 (HC‐3) (50–400 μg/ml) inhibited contractions or relaxations produced by TMA but not contractions produced by acetylcholine. The inhibition was rapid in onset and readily reversible. Contractions produced by transmural stimulation were unaffected by HC‐3 but responses produced by nicotine were inhibited.
Low concentrations of hyoscine and benzhexol inhibited responses to acetylcholine to a greater extent than those to TMA.
Morphine, raised concentrations of Mg++ or reduced concentrations of Ca++ inhibited contractions produced by TMA and by acetylcholine to a similar extent.
Edrophonium, in concentrations which preferentially inhibit acetylcholinesterase, increased contractions produced by acetylcholine and converted responses to nicotine or transmural stimulation into contractions or biphasic responses with a marked contraction phase but did not increase contractions produced by TMA.
Iso‐OMPA, in concentrations which preferentially inhibit butyrylcholinesterase, had no effect on responses to acetylcholine, nicotine, transmural stimulation or TMA.
HC‐3 inhibited contractions produced by TMA in the presence of anticholinesterases but had little effect on contractions produced by acetylcholine.
These results suggest that TMA produces contractions by acting directly on receptors of the smooth muscle. An analysis of possible reasons for HC‐3 (in the concentrations used) acting as an antagonist of TMA but not of acetylcholine indicates that the findings do not necessarily contradict the interpretation that both agonists act on the same receptor.
Cardiovascular reactivity in the experimental hypertensive rat
Authors: FINCH L. 
Published: July 2012

Summary
In pithed preparations, deoxycorticosterone (DOCA)/NaCl‐induced hypertensive rats showed increased cardiovascular reactivity to injected noradrenaline, DMPP, tyramine, angiotensin and to sympathetic nerve stimulation.
Pithed, chronic renal hypertensive rats showed similar hyperreactivity to noradrenaline, DMPP and tyramine but responses to sympathetic nerve stimulation were within normal limits.
In the isolated, Krebs perfused mesentery preparation, vessels obtained from both DOCA/NaCl and renal hypertensive rats showed hyperreactivity to injected noradrenaline. Responses to periarterial nerve stimulation were also markedly increased in preparations from DOCA/NaCl hypertensive rats, while preparations from renal hypertensive rats showed this effect only at higher rates of stimulation (12 and 25 Hz).
Effects of some polymethylene bis(hydroxyethyl) dimethylammonium compounds on acetylcholine synthesis
Authors: HEMSWORTH B. A. 
Published: July 2012

Summary
The effects of some polymethylene bis(hydroxyethyl)dimethylammonium compounds have been studied on acetylcholine (ACh) synthesis and as substrates for choline acetyltransferase (ChAc).
The decamethylene analogue (C10‐dichol) inhibited ACh synthesis by mitochondrial (P2) fractions of guinea‐pig cerebral cortex suspended in Tris buffer but had no effect on ACh synthesis by P2 fractions when the membranes surrounding the ChAc enzyme were broken down by homogenization in Triton X‐100.
C10‐Dichol was acetylated by ChAc almost to the same extent as choline. The initial rate of acetylation, at a concentration of 10−3m, was more rapid than for choline; however, the apparent Michaelis‐Menten constant for C10‐dichol was greater than the Km for choline, showing a lower affinity for the ChAc enzyme.
All the dicholine compounds were acetylated to some extent by ChAc and the rate of acetylation increased with an increase in the length of the methylene chain between the two quaternary nitrogen atoms in each dicholine molecule.
The rate of acetylation of the dicholine compounds paralleled the activity of these analogues at the prejunctional site at the neuromuscular junction. The possibility is suggested that part of the pharmacological activity of these compounds may be due to their incorporation into cholinergic nerve endings followed by acetylation by ChAc before subsequent release as a false transmitter.
Depletion of brain noradrenaline and dopamine by 6‐hydroxydopamine
Authors: BREESE G. R. , TRAYLOR T. D. 
Published: July 2012

Summary
After intracisternal administration, 6‐hydroxydopamine had a greater effect on brain noradrenaline than on dopamine.
Administration of two doses of 6‐hydroxydopamine increased the depletion of noradrenaline but not of dopamine.
Small doses of 6‐hydroxydopamine decreased the concentration of noradrenaline with little or no effect on dopamine. Tyrosine hydroxylase activity was not reduced with these treatments.
While pargyline pretreatment offered no advantage in the depletion of brain noradrenaline after 6‐hydroxydopamine, depletion of brain dopamine was greatly potentiated by this treatment. The reduction of striatal tyrosine hydroxylase activity observed after 6‐hydroxydopamine was also potentiated by pargyline pretreatment.
The amounts of labelled noradrenaline and dopamine formed from 3H‐tyrosine were greatly reduced by 6‐hydroxydopamine treatment. After 3H‐DOPA, formation of noradrenaline was greatly reduced while formation of labelled dopamine was only moderately reduced suggesting that decarboxylation of DOPA can occur in other than catecholamine containing neurones.
Desmethylimipramine and imipramine inhibited depletion of noradrenaline produced by 6‐hydroxydopamine but did not alter depletion of dopamine. Reserpine did not inhibit depletion of catecholamines produced by 6‐hydroxydopamine.
Administration of 6‐hydroxydopamine to developing rats lowered both noradrenaline and dopamine concentrations as well as the tyrosine hydroxylase activity in the brains of these animals.
Accumulation of quinidine by human blood platelets: effects on platelet ultrastructure and 5‐hydroxytryptamine
Authors: BOULLIN D. J. , O'BRIEN R. A. 
Published: July 2012

Summary
We have studied the mechanism of quinidine uptake by normal human blood platelets.
Platelets in plasma or Krebs solution took up quinidine extremely rapidly, the maximal drug concentration ratio of platelet to medium being 24 to 1 after 1 minute.
The effects of metabolic inhibitors on uptake were equivocal. Ouabain had no effect but iodoacetate and dinitrophenol were effective. However, as accumulation was not inhibited by low temperature, it was probably not energy dependent.
Interactions between quinidine and 5‐HT were also investigated.
Quinidine blocked 5‐HT uptake, but conversely, neither 5‐HT itself nor 5‐HT uptake inhibitors, such as cocaine, dexamphetamine, and desipramine interfered with quinidine accumulation.
Electronmicrographs of platelets incubated with 10−5, 10−4 or 2 × 10−3m quinidine in Krebs solution for 2 h showed no changes at the lower concentrations, but gross ultastructural damage, including disintegration of the plasma membrane, at 2 × 10−3m.
Further evidence for intracellular penetration was obtained because quinidine released endogenous 5‐HT and ATP, and also 14C‐5‐HT from loaded cells.
We conclude that quinidine is taken up by the platelet by a passive process, unrelated to the 5‐HT transport mechanism. It is probably accumulated largely in the plasma membrane and outer protein layer, but intracellular penetration and ultrastructural damage may occur.
Although the effects on 5‐HT and ATP were not due to platelet damage, this may occur in vivo and be the cause of quinidine induced thrombocytopenic purpura.
Investigation of central cholinergic mechanisms in the conscious mouse
Authors: ANKIER S. I. , BRITTAIN R. T. , JACK D. 
Published: July 2012

Summary
An investigation of central cholinoceptors in the mouse has been made by injecting cholinomimetic drugs into the cerebral ventricles and seeing how their effects were modified by prior administration of atropine‐like substances and other drugs.
Carbachol or oxotremorine injected in small doses intracerebroventricularly into conscious mice caused hypothermia, gross tremor and a variety of parasympathomimetic effects including lachrymation and salivation. Acetylcholine injected in this way was active only in much larger doses.
Methacholine and pilocarpine also caused a variety of parasympathomimetic effects after intracerebroventricular injection but virtually no hypothermia or tremor.
Nicotine injected intracerebroventricularly caused mild hypothermia, fine tremor but no parasympathomimetic effects.
Atropine‐like drugs, tricyclic antidepressants and amphetamine antagonized the hypothermia induced by intracerebroventricular carbachol or oxotremorine.
The sites of action of the atropine‐like drugs are in the brain; those of the tricyclic antidepressants and amphetamine are in the periphery probably on heat generating β‐adrenoceptor mechanisms.
It is concluded that the atropine sensitive cholinoceptors in the brain vary in their sensitivities to cholinomimetic drugs, other than acetylcholine, and may exist in isoreceptor forms.
Peripheral atropine sensitive cholinoceptors may also exist in isoreceptor forms.
Cat assay for the emetic action of digitalis and related glycosides (digitoxin, digoxin, lanatoside C, ouabain and calactin)
Authors: PARSONS J. A. , SUMMERS R. J. 
Published: July 2012

Summary
A titration assay with two end points is described for comparison of the emetic and lethal potencies of digitalis‐like drugs.
A drug was infused at constant rate to a conscious, unrestrained cat, through an indwelling venous cannula. At the moment of vomiting the cat was rapidly anaesthetized and infusion continued at the same rate until the moment of cardiac arrest.
With very slow and very fast infusions, the emetic and lethal doses tended to rise. In the range between these extremes (which varied from drug to drug) they were independent of time.
The observations could be accounted for by analogue computation, assuming that the drugs entered an initial pool and were distributed at finite rates to receptors in the CNS (vomiting centre) and heart.
Half times of metabolic loss derived from this computation for digitoxin, digoxin and ouabain (17, 9·9 and 1·8 h, respectively) were in the same ratio as the threefold longer half times reported for these drugs in man.
When measured with infusion rates in the time independent range, the ratio of lethal to emetic doses did not vary between the drugs studied. All caused vomiting at 40% of the lethal dose.
From a review of the literature, the emetic and cardiotoxic actions of digitalis‐like drugs appear inseparable and probably share a common biochemical mechanism.
It is concluded that foreseeable improvements in digitalis‐like drugs are small and would depend on the elimination of any local emetic effect on gut receptors which they may have.
Effects of adrenoceptor blocking agents on body temperature
Authors: FELDBERG W. , SAXENA P. N. 
Published: July 2012

Summary
The effect on rectal temperature of adrenoceptor blocking agents, injected through a cannula chronically implanted into a lateral cerebral ventricle, was examined in unanaesthetized rabbits, cats and rats, kept at room temperature (19–22° C).
In rabbits, the α‐adrenoceptor blocking agent phenoxybenzamine (50 or 100 μg) produced marked hypothermia when injected intraventricularly but not when injected intravenously. In some rabbits as little as 1 μg was effective on intraventricular injection. Phentolamine and ergotamine, the other α‐adrenoceptor blocking agents examined, had a much weaker hypothermic action when injected intraventricularly, whereas the β‐adrenoceptor blocking agents propranolol, pronethalol and Trasicor had no effect.
In rabbits in which the noradrenaline stores of the hypothalamus were depleted by intraventricular injections of reserpine, the hypothermic effect of phenoxybenzamine was abolished and remained abolished for a few days.
In cats, an intraventricular injection of phenoxybenzamine (200 μg) produced long‐lasting hyperthermia, but not in all cats, and only with the first, or the first two or three injections. Injected intraperitoneally, this dose had no effect on temperature. Phentolamine (100 or 200 μg) had a very weak hyperthermic effect and phentolamine (500 μg), a hypothermic effect, but only on intraventricular injection, whereas ergotamine (100 and 200 μg) had a weak hyperthermic effect both on intraventricular and intraperitoneal injection. Propranolol and Trasicor had no effect on temperature when injected intraventricularly.
In rats, phenoxybenzamine (5 or 20 μg) produced long‐lasting hypothermia on intraventricular injection.
Some of the temperature effects produced by intraventricular injections of the α‐adrenoceptor blocking agents are explained on the assumption that they prevent the effect on temperature produced by a continuous release of noradrenaline from adrenergic neurones innervating the anterior hypothalamus.
3H‐Noradrenaline‐accumulating ability of cholinergic nerve terminals in cat sympathetic ganglia
Authors: GRAHAM J. D. P. , IVENS CAROLINE , JOÓ F. , LEVER J. D. , MOTTRAM D. R. , SPRIGGS T. L. B. 
Published: July 2012

Summary
After incubation of pieces of cat posterior mesenteric ganglion in [3H]‐noradrenaline solution, the localization of the isotope was assessed by electronautoradiography.
Significantly higher concentrations of [3H]‐noradrenaline were found over acetylcholinesterase‐positive axons terminal on ganglion cells than in adjacent background areas.
[3H]‐Noradrenaline was not accumulated by ganglion cells under these circumstances.
The significance of these findings in relation to previous physiological and pharmacological investigation is discussed.
Comparison of the effects of drugs on the aggregation of hamster platelets in vivo and in vitro
Authors: BEGENT NICOLA A. , BORN G. V. R. 
Published: July 2012

Summary
A method is described for measuring the inhibitory effectiveness of drugs on the aggregation by ADP of hamster platelets in vivo.
The method was used to compare the effects of several drugs, viz. adenosine, imipramine, desmethylimipramine and aspirin, on platelet aggregation in vivo with their in vitro effects measured photometrically.
The concentrations of adenosine and imipramine present in the cheek pouch after 10 min infusions were measured using radioactively labelled drugs.
The results show that adenosine (0·4 μm) inhibited platelet aggregation in vivo by 43%, whereas several times this concentration was required to produce the same inhibition in vitro.
Imipramine and desmethylimipramine (0·4 μm) did not inhibit platelet aggregation in vivo; in vitro, however, desmethylimipramine caused up to 34% inhibition at concentrations as low at 0·25 μm.
Aspirin (estimated 0·2 mm) inhibited platelet aggregation in vivo by 37% whereas similar inhibition in vitro required about 1 mm aspirin. Sodium salicylate was several times less potent than aspirin in vivo.
Effects of isoxazolium cations on some isolated muscle preparations
Authors: MITTAG T. W. , TORMAY ANNE 
Published: July 2012

Summary
The quaternary ammonium compound, N,t‐butyl‐5‐methyl isoxazolium perchlorate (BIP), an anionic group reagent, initially causes contractions of the rat phrenic‐nerve diaphragm, guinea‐pig ileum and rabbit aortic strip preparations in vitro.
In addition, the drug produces an irreversible block of indirectly elicited twitch responses in the diaphragm and of contractions induced by acetylcholine, methylfurmethide, dimethyl‐phenylpiperazinium, 5‐hydroxytryptamine (5‐HT), histamine, angiotensin and pilocarpine in the ileum, while direct electrical stimulation of the diaphragm and contractions of the ileum to Ba and K ions are relatively unaffected.
BIP is also an irreversible inhibitor of acetylcholinesterase but not of butyrylcholinesterase.
On rabbit aortic strip preparations, responses to histamine, noradrenaline and 5‐HT were differentially sensitive to irreversible blockade by BIP.
Diphenhydramine, used in conditions which gave complete protection of the histamine response to irreversible block by dibenamine, did not protect against the blocking action of BIP but increased the blockade.
These results suggest that BIP reacts covalently with anionic groups which mediate receptor initiated stimuli. The isoxazolium group may be useful in conferring irreversible properties by its substitution in drug molecules for the pyrrole or pyrrolidine group.