bluuebunny/crossref_metadata_2025_split huggingface dataset:
Origin of the after‐hyperpolarization that follows removal of depolarizing agents from the isolated superior cervical ganglion of the rat
Authors: BROWN D. A. , BROWNSTEIN M. J. , SCHOLFIELD C. N. 
Published: July 2012

Summary
Potential changes in isolated rat superior cervical ganglia following addition and removal of depolarizing agents were recorded using a moving‐fluid extracellular electrode system.
Ganglionic negativity produced by carbachol was followed by a pronounced ganglionic positivity on washing. This after‐positivity was attributed to hyperpolarization of the ganglion cells since it was unaffected by crushing the postganglionic trunk.
The after‐hyperpolarization was selectively depressed by (a) cooling (Q10 2·3), (b) metabolic inhibitors (cyanide, azide, 2,4‐dinitrophenol), (c) reducing [K+]o or substituting Cs+ for K+, (d) ouabain, and (e) substituting Li+ for Na+. This suggested a close dependence on active Na+ transport.
When K+ was restored to K+‐free solution, or the preparation was warmed rapidly, or when metabolic inhibitors were washed away, the hyperpolarization was rapidly regenerated. The effect of restoring K+ indicated that the hyperpolarization was generated directly by the Na+ pump.
The hyperpolarization was not altered by replacing CI− with isethionate, indicating that the voltage change produced by the Na+ current was not modified by passive CI− movements.
Hexamethonium added to the washout fluid augmented the after‐hyperpolarization, suggesting that there was a high (cationic) leak current due to continued receptor‐activation on washing with normal Krebs solution.
The hyperpolarization was reduced by omission of Ca2+ and restored by addition of Mg2+. This was considered to result from changes in passive membrane permeability.
The time‐course of post‐carbachol hyperpolarization accorded with a Na+ extrusion process whose rate was directly proportional to [Na+]i with a rate constant of 0·38 ± 0·02 min−1 at 23–27° C.
With increasing concentrations of carbachol, the amplitude of the hyperpolarization increased in proportion to the preceding depolarization, but the rate constant of the hyperpolarization was unchanged.
The after‐hyperpolarization was reduced in proportion to the depolarization by hexamethonium, but was not affected by atropine, hyoscine or tetrodotoxin.
A hyperpolarization also followed depolarization by acetylcholine or by EDTA in Ca2+‐free solution.
Nicotine‐depolarization was not followed by a hyperpolarization unless hexamethonium was added to the washout fluid. This was attributed to prolonged receptor‐stimulation by nicotine.
It was concluded that the after‐hyperpolarization was due to the electrogenic extrusion of Na+ accumulated in the ganglion cells during the preceding depolarization, with no involvement of specific muscarinic receptors. The relationship of this process to post‐tetanic hyperpolarization and to other forms of drug‐induced ganglionic hyperpolarization is discussed.
Role of the α‐adrenoceptor in regulating noradrenaline overflow by nerve stimulation
Authors: ENERO MARÍA A. , LANGER S. Z. , ROTHLIN R. P. , STEFANO F. J. E. 
Published: July 2012

Summary
A study of the actions of phenoxybenzamine on transmitter overflow, neuronal and extraneuronal uptake of noradrenaline and in causing α‐adrenoceptor blockade was carried out using the isolated cat nictitating membrane preparation.
Phenoxybenzamine increased transmitter overflow elicited by nerve‐stimulation at 10 Hz in a concentration dependent manner in the range 10−8 to 10−5 g/ml.
Neuronal uptake of [3H]‐noradrenaline was not inhibited by concentrations lower than 10−6 g/ml of phenoxybenzamine. With 10−7 g/ml of phenoxybenzamine a significant increase in transmitter overflow was obtained, although neuronal uptake of noradrenaline was not affected. Higher concentrations of phenoxybenzamine (10−6 and 10−5 g/ml) inhibited the neuronal uptake of noradrenaline and further increased transmitter overflow.
Extraneuronal uptake of [3H]‐noradrenaline was inhibited only with the highest concentration of phenoxybenzamine tested (10−5 g/ml) and therefore appears to be unrelated to the effects on transmitter overflow.
There was a significant correlation between the degree of α‐adrenoceptor block produced by phenoxybenzamine and the increase in transmitter overflow obtained by nerve stimulation.
These results indicate that phenoxybenzamine, in addition to increasing overflow by preventing reuptake of noradrenaline, may increase transmitter release.
The possibility that phenoxybenzamine acts on α‐adrenoceptors in the adrenergic nerve terminal is discussed. These receptors would be involved in a negative feedback mechanism regulating transmitter release.
Modification by prostaglandin E2 (PGE2) of the response of guinea‐pig isolated vasa deferentia and atria to adrenergic stimuli
Authors: BHAGAT B. , DHALLA N. S. , GINN DONNA , La MONTAGNE A. E. , MONTIER A. D. 
Published: July 2012

Summary
Prostaglandin E2 (PGE2) exerted positive cardiostimulant effects on isolated guinea‐pig atria. The response was not altered by treatment of the animal with reserpine or by addition of propranolol to the organ bath. These results suggest that the cardiostimulatory actions of PGE2 are not mediated through the release of catecholamines or stimulation of adrenoceptors.
On the electrically driven atria, PGE2 consistently exerted a cardiostimulant action which was not appreciably altered by changes in calcium ion in the bathing medium. PGE2 showed no effect on the transport of calcium by the fragments of heart sarcoplasmic reticulum.
PGE2 reduced the responses to both noradrenaline and tyramine in the isolated atria. The shifted dose‐response curve was not parallel to the original.
PGE2 increased the contractor response of the isolated vas deferens to nerve stimulation or to direct electrical stimulation.
PGE2 antagonized the increase caused by noradrenaline in contractor response of isolated vas deferens to direct electrical stimulation, whereas it affected the potentiation by noradrenaline differently when the vas deferens was contracting in response to nerve stimulation. In low concentration it inhibited and in large concentrations, it slightly enhanced the potentiation by catecholamine.
It is concluded that PGE2 has actions on multiple sites. It has postjunctional as well as pre‐junctional effects on adrenergic neurones.
Morphine‐induced kinetic alterations of choline acetyltransferase of the rat caudate nucleus
Authors: DATTA K. , WAJDA I. J. 
Published: July 2012

Summary
In order to explain the decrease of choline acetyltransferase (2.3.1.6.) activity observed in the caudate nucleus of morphine‐treated rats, partially purified preparations of the enzyme were used in kinetic studies, with choline as substrate.
The apparent Michaelis constant for the enzyme obtained from normal rats was found to be 0·9 mm choline; this value doubled when the animals were killed one hour after a single injection of morphine (30 mg/kg). When the rats were injected daily for 4 or 15 days, and killed one hour after the last injection, the apparent Km value was 2·1 mm in each case. Prolonged daily treatment with morphine, followed by 48 h withdrawal, or by administration of 4 mg/kg of naloxone (given half an hour after the last injection of morphine) resulted in apparent Km values of 1·3–1·5 mm of choline, suggesting a gradual return to the lower, normal substrate requirement. Vmax changes were insignificant.
The effect of morphine added in vitro to different enzyme preparations was also studied. The Km values of 0·9 mm, in the enzyme isolated from normal rats, increased to 2·0 after incubation in vitro with 12·5 mm morphine. Similar increases were found in enzymes obtained from rats 48 h after the withdrawal of morphine or from rats injected with naloxone after prolonged morphine treatment. The high apparent Km values, found in enzyme obtained from animals killed one hour after the last dose of morphine, did not change upon incubation with 12·5 mm morphine. A similar pattern of Km changes was noticed after incubation with 25 mm acetylcholine.
An increase of 32% in acetylcholine (ACh) level was found in the caudate nucleus one hour after subcutaneous injection of 30 mg/kg of morphine. Return to normal values was observed when morphine was administered daily. After two to three weeks of daily treatment and subsequent withdrawal from morphine for 48 h, the levels of ACh were normal. If the daily treated rats were given naloxone within half an hour of the last injection of morphine, and killed 30 min later, the levels of ACh remained normal.
Fifty per cent inhibition of enzyme activity was observed upon in vitro incubation with 75 mm acetylcholine, or with 25 mm morphine. The same degree of inhibition was noticed when the enzyme was obtained from normal or from morphine‐treated rats.
Effects of amphetamine on the turnover rate of brain catecholamines and motor activity
Authors: COSTA E. , GROPPETTI A. , NAIMZADA M. K. 
Published: July 2012

Summary
Rats receiving (+)‐amphetamine (either 0·3 or 0·2 mg/kg, i.v.) are anorexic. Only the former dose increases their motor activity. Both doses fail to change dopamine (DM) and noradrenaline (NA) concentrations in striatum and teldiencephalon. The turnover rate of striatal DM is increased only by 0·3 mg/kg of (+)‐amphetamine; neither dose changes NA turnover rate in teldiencephalon.
(—)‐Amphetamine (1 mg/kg, i.v.) causes anorexia and hyperthermia in rats but it changes neither the steady‐state concentration nor the turnover rate of striatal DM and tel‐diencephalic NA. Motor activity is not increased by this dose of (—)‐amphetamine.
Cocaine (3 mg/kg, i.v.) increases motor activity and accelerates the turnover rate of striatal DM. This drug neither accelerates turnover rate of tel‐diencephalic NA nor causes anorexia.
These observations suggest that the acceleration of striatal DM turnover rate elicited by (+)‐amphetamine and cocaine may be associated with an effect on motor activity. In contrast, the increase of motor activity seems unrelated to the effects of these drugs on noradrenergic tracts of the teldiencephalon.
Role of cardiotoxin and phospholipase A in the blockade of nerve conduction and depolarization of skeletal muscle induced by cobra venom
Authors: CHANG C. C. , CHUANG SING‐TAI , LEE C. Y. , WEI J. W. 
Published: July 2012

Summary
The effects of phospholipase A (PhA), cardiotoxin (CTX) and neurotoxin (cobrotoxin) isolated from Formosan cobra (Naja naja atra) venom on conduction of the rat phrenic nerve and membrane potential of the rat diaphragm were studied.
Phospholipase A, lysolecithin and cobrotoxin were without effect on the axonal conduction. Cardiotoxin was the only active agent in cobra venom, but it was less potent than the crude venom.
The blocking action of cardiotoxin was markedly accelerated by the simultaneous administration of phospholipase A. However, the minimum effective concentration of cardiotoxin (100 μg/ml), was not decreased by phospholipase A. Pretreatment of the nerve with phospholipase A, followed by washout, did not alter the activity of cardiotoxin.
Cardiotoxin (3 μg/ml) completely depolarized the membrane of superficial muscle fibres within 60 min, being 3 times more potent than the crude venom. Phospholipase A, on the other hand, needed a dose 30 times higher and a prolonged period of incubation to induce depolarization of similar extent. Cobrotoxin was without effect on membrane potentials.
CaCl2 (10 mm) effectively antagonized the nerve blocking as well as the depolarizing effect of the crude venom, cardiotoxin or cardiotoxin plus phospholipase A. By contrast, the slow depolarizing effect of phospholipase A was enhanced by high concentrations of calcium.
Cardiotoxic fractions of Indian cobra venom affected both nerve conduction and diaphragm membrane potential in exactly the same way as cardiotoxin. Toxin A of the same venom was without effect.
It is concluded that the active agent in cobra venoms either on axonal conduction or on muscle membrane is cardiotoxin. The synergistic effect of phospholipase A on cardiotoxin appears to be due to acceleration rather than potentiation of its action. The mechanism of action of cardiotoxin and its synergism by phospholipase A are discussed.
The central action of clonidine and its antagonism
Authors: KATIC FRANCES , LAVERY HELEN , LOWE R. D. 
Published: July 2012

Summary
We have examined the central actions of clonidine (2‐(2–6‐dichlorphenylamine)‐2‐imidazoline hydrochloride). It has been confirmed that when infused into the vertebral artery at 2 μg/min, it caused a decrease in blood pressure and a slight increase in heart rate. The same dose given intravenously or into the carotid artery had no effect.
Intravertebral clonidine also greatly reduced the reflex response to carotid occlusion and the effects of an intravertebral infusion of angiotensin (1 ng/kg)/min.
This central action of clonidine was antagonized by the adrenergic neurone blocking drug bethanidine (4–5 mg/kg intravenously) even after the cervical cord had been transected at C4–C6 suggesting that bethanidine also has central actions.
Other drugs which also antagonized the central effects of clonidine were guanethidine (4–5 mg/kg intravenously), bretylium (10 mg/kg intravenously) and phentolamine (0·2 mg/kg intravenously).
It is suggested that there are central adrenergic neurones which inhibit cardiovascular autonomic reflexes and that the central autonomic effects of clonidine are due to stimulation of inhibitory adrenoceptors. The antagonism by adrenergic neurone blocking drugs of the effect of clonidine could therefore be due to blockade of these inhibitory pathways.
The central action of clonidine could only be demonstrated when a high concentration was infused into the vertebral artery and could not be shown with oral doses of (20 μg/kg)/day for seven days. It is concluded that the hypotensive action of therapeutic doses is unlikely to be due to the central action of clonidine.
The action of bombesin on the systemic arterial blood pressure of some experimental animals
Authors: ERSPAMER V. , MELCHIORRI P. , SOPRANZI N. 
Published: July 2012

Summary
The changes in blood pressure in response to parenteral administration of bombesin, the active tetradecapeptide of the skin of the European discoglossid frogs Bombina bombina and Bombina variegata variegata have been investigated in some experimental animals.
In most species, the polypeptide elicited hypertension which was usually gradual in onset and slow to disappear. Blood pressure increases rarely exceeded 40–50 mmHg. At the beginning of an experiment some dose‐response relationship could often be observed, but later tachyphylaxis developed. During an intravenous infusion of bombesin the rise in blood pressure could sometimes be maintained at a steady level as long as the infusion was continued, but at other times, the rise of pressure slowly subsided with continued administration of the polypeptide. In the rat and the chicken hypertension elicited by high doses of bombesin was often followed by secondary hypotension.
Bombesin‐induced hypertension was apparently not affected by pretreatment with either α‐ or β‐adrenergic blocking agents. Similarly secondary hypotension was not abolished by atropine. Thus, the effect of bombesin on vascular smooth muscle seems to be predominantly a direct one.
Angiotensin was usually more potent than bombesin, and its effect on blood pressure was more rapid and of shorter duration. Tachyphylaxis to angiotensin was lacking or moderate.
In sharp contrast to the other species, the monkey responded to bombesin with frank hypotension, which was usually proportional to the dose. In the monkey the hypotensive effect of bombesin was equal to, or greater than that of eledoisin or physalaemin and bombesin‐induced hypotension was of longer duration than that of the other polypeptides. Tachyphylaxis was moderate for low and adequately spaced doses of the polypeptide, but prompt and intense for high doses. Long‐lasting hypotension was obtained by intravenous infusion of bombesin, but repeated infusions caused tachyphylaxis. Bombesin‐induced hypotension was not affected by pretreatment with atropine.
Bombesin may be easily distinguished from all other known peptides active on vascular and extravascular smooth muscle by its effects on blood pressure. This does not apply to bombesin‐like peptides, such as alytesin and ranatensin.
Acetylcholine inhibition in the intact and chronically isolated cerebral cortex
Authors: JORDAN L. M. , PHILLIS J. W. 
Published: July 2012

Summary
Some spontaneously firing cells in the cerebral cortex of cats can be depressed by iontophoretically applied acetylcholine or acetyl‐β‐methylcholine, and this depression is antagonized by atropine. Thirteen per cent of 101 spontaneously active neurones tested were depressed by cholinergic agents and 64% were excited.
Single stimuli applied to the adjacent cortical surface excited 132 neurones orthodromically. Acetylcholine or acetyl‐β‐methylcholine depressed this synaptic firing in 18% of the cells. The depression was blocked by atropine.
The population of neurones in which cholinergic agents depressed spontaneous or synaptic firing was located within the superficial half of the cortex.
Glutamate‐induced firing was depressed by cholinergic agents in 41% of 211 cells tested; atropine and strychnine strongly antagonized this depressant action, while dihydro‐β‐erythroidine was a weaker antagonist.
Long duration inhibition of glutamate‐induced firing evoked by repetitive stimulation of the cortical surface could be blocked by atropine or strychnine in both the intact and chronically isolated cortex. This provides strong evidence for a system of intracortical cholinergic neurones which make direct inhibitory contacts with neurones in the superficial layers of the cortex.
Drug‐metabolizing capacity in states of drug dependence and withdrawal
Authors: BALLINGER B. , BROWNING M. , O'MALLEY K. , STEVENSON I. H. 
Published: July 2012

Summary
Drug‐metabolizing capacity was assessed in 8 barbiturate‐dependent and in 3 Mandrax‐dependent patients using, as indices, plasma antipyrine half‐life and in some cases urinary output of 6β‐hydroxycortisol. For comparison, antipyrine half‐life was also measured in volunteers before and after a period of taking hypnotic doses of these agents.
Both indices indicated a very high drug‐metabolizing capacity in the dependent subjects on admission, the antipyrine half‐life value in the barbiturate patients being the shortest reported to date for any drug‐exposed group. The urinary output of 6β‐hydroxycortisol was approximately three times that in a control population.
This induction of drug‐metabolizing capacity presumably contributed to the marked drug tolerance observed in the dependent patients.
It appeared that drug‐metabolizing capacity eventually returned to normal levels after withdrawal of the barbiturate.
It is concluded that the abnormal drug‐metabolizing capacity of dependent patients must be taken into account in assessing dose requirements for other drugs.
Species and ionic influences on the accumulation of digitalis glycosides by isolated perfused hearts
Authors: DUTTA S. , MARKS B. H. 
Published: July 2012

Summary
The ability of isolated perfused guinea‐pig (digitalis‐sensitive species) and rat (digitalis‐resistant species) hearts to accumulate radio‐labelled digitalis glycosides was studied in relation to the ionic composition of the perfusion medium.
It was observed that in both species much less digoxin was accumulated than was digitoxin or proscillaridin.
The accumulation of digoxin was markedly inhibited in a low sodium or in high potassium medium. These effects were similar, but relatively less marked, with digitoxin and proscillaridin. Calcium and magnesium removal had relatively smaller effects on the accumulation of both polar and non‐polar glycosides.
The low accumulation of all digitaloids by the rat heart in comparison to the guinea‐pig heart may be due to the formation of unstable complexes between the cellular membranes in the rat heart and the various digitaloids used in this study. Although digitaloids have a reduced affinity for rat hearts and rat heart membranes in comparison to guinea‐pigs, the order of the accumulation of different glycosides in both species is the same, i.e. much less with polar glycosides than with non‐polar glycosides.
It was concluded that non‐polar glycosides such as digitoxin and proscillaridin demonstrate the same ion‐dependent accumulation mechanism as do the more polar glycosides such as digoxin and ouabain. In addition, the non‐polar glycosides possess high capacity for ion‐independent binding presumably due to lipophilic interactions with membranes.
The role of 5‐hydroxytryptamine and noradrenaline in the hyperthermic reaction induced by pethidine in rabbits pretreated with pargyline
Authors: FAHIM I. , ISMAIL M. , OSMAN O. H. 
Published: July 2012

Summary
Inhibition of 5‐hydroxytryptamine (5‐HT) synthesis by p‐chlorphenylalanine protected rabbits pretreated with pargyline from the fatal hyperthermic reaction which occurs on the intravenous injection of pethidine.
The development of tolerance to morphine did not protect against the fatal pargyline‐pethidine hyperpyrexia. Moreover, the injection of nalorphine before or after pethidine conferred no protection.
Pethidine evoked a hyperpyrexia in rabbits pretreated with lithium sulphate or yohimbine.
Sodium diethyldithiocarbamate caused a fatal hyperpyrexia in rabbits pretreated with pargyline.
It is concluded that the pargyline‐pethidine hyperthermic interaction might involve the relative concentrations of 5‐HT and noradrenaline in the hypothalamus.
Metabolism of isoprenaline in dog and man
Authors: CONOLLY M. E. , DAVIES D. S. , DOLLERY C. T. , MORGAN C. D. , PATERSON J. W. , SANDLER M. 
Published: July 2012

Summary
The metabolism of isoprenaline has been studied in man and dog following intravenous and oral or intra‐duodenal administration.
Intravenous isoprenaline was excreted largely unchanged in urine in both species. Only one‐third of the radioactivity in urine was in the form of the O‐methyl metabolite.
After oral doses in man or intraduodenal doses in dogs, plasma radioactivity was almost entirely as conjugated isoprenaline and this metabolite accounted for more than 80% of radioactivity in urine.
Catechol‐O‐methyl transferase may be less important than Uptake2 in limiting the pharmacological action of isoprenaline.
Pharmacological response (heart‐rate increase) was related to plasma concentration of isoprenaline only after rapid intravenous injections. In dogs, following prolonged infusion or intraduodenal doses, heart rate returned to base‐line values when plasma concentrations of isoprenaline were high.