bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mode of action of α‐methylnoradrenaline on temperature and oxygen consumption in young chickens
Authors: ALLEN D. J. , GARG K. N. , MARLEY E. 
Published: July 2012

Summary
Temperature, oxygen consumption, electromyographic activity, plasma non‐esterified fatty acids and blood sugar were estimated in conscious unrestrained young chickens under conditions of thermoneutrality (31° C) and below thermoneutrality (16° C). In some chickens carotid arterial pressure was also recorded.
At thermoneutrality, α‐methylnoradrenaline lowered temperature and oxygen consumption in intact or chronically vagotomized chicks. α‐Methylnoradrenaline was ineffective on temperature in chicks with transection of the brain‐stem posterior to the hypothalamus but anterior to the respiratory centre. Hypothermia due to α‐methylnoradrenaline was associated with a significant reduction of plasma non‐esterified fatty acids but blood sugar was not significantly altered. Lowering of temperature by α‐methylnoradrenaline occurred despite vasoconstriction which would hinder heat loss.
Temperature and oxygen consumption were reduced by α‐methylnoradrenaline in chronically thyroidectomized chicks to the same extent as in intact chicks but recovery did not occur unless the chicks were taken from the metabolism chamber and warmed artificially. In contrast, chronically thyroidectomized chicks given replacement thyroxine were relatively resistant to α‐methylnoradrenaline.
Oxygen consumption of tissue slices from different parts of the chick's brain, including the diencephalon, was not altered by α‐methylnoradrenaline over an extensive dose range. The effects of α‐methylnoradrenaline on temperature and oxygen consumption in intact chickens were unlikely, therefore, to be due to depressed metabolism of neurones.
In an environment below thermoneutrality (16° C) temperature was considerably reduced and carotid arterial pressure fell 40–50 mmHg. In contrast, electromyographic activity, oxygen consumption and plasma non‐esterified fatty acids were markedly raised whereas blood sugar was insignificantly elevated.
In experiments at 16° C, α‐methylnoradrenaline markedly reduced oxygen consumption although values were still higher than those at thermoneutrality. Temperature fell further, but whereas the reductions in oxygen consumption and temperature were long‐lasting, electromyographic activity (shivering) was only transiently diminished. Plasma non‐esterified fatty acids were reduced after α‐methylnoradrenaline but not significantly so; blood sugar was not significantly altered. The time‐course for recovery of oxygen consumption following α‐methylnoradrenaline paralleled recovery from its blood pressure effects but the effect on oxygen consumption was not a consequence of the blood pressure changes. The effects of α‐methylnoradrenaline on temperature, oxygen consumption and electromyographic activity were similar to those of another central depressant, pentobarbitone.
Temperature responses and other effects of 5‐hydroxytryptophan and 5‐hydroxytryptamine when acting from the liquor space in unanaesthetized rabbits
Authors: BANERJEE U. , BURKS T. F. , FELDBERG W. , GOODRICH CECILIE A. 
Published: July 2012

Summary
In unanaesthetized rabbits 5‐hydroxytryptophan (5‐HTP) and 5‐hydroxytryptamine (5‐HT) were injected into the cisterna magna or into the cannulated left lateral cerebral ventricle while rectal temperature was recorded.
5‐HTP injected intracisternally in a dose of 1·5–3 mg produced a fall in temperature often followed by a rise beyond the pre‐injection level. With 6 mg the main effect was a rise in temperature. The intraventricular injection of 1–2 mg 5‐HTP usually produced a fall followed by a rise.
5‐HT injected intracisternally in a dose of 0·2 mg produced a fall in temperature similar to that produced with this dose injected intraventricularly. Following an intracisternal injection of 1–4 mg 5‐HT there was either a fall, or a fall followed by a rise, but in a few experiments the effect consisted mainly of a rise in temperature.
Additional effects regularly observed with these injections were tachypnoea, ear twitching, rapid movements of the vibrissae, shaking of the head, wiping and scratching movements, ataxia, nodding and sideways movements of the head and long‐lasting catalepsy.
The sites where 5‐HTP and 5‐HT act when producing the temperature responses and the various behavioural effects are discussed.
The effect of betamethasone on circadian and stress‐induced pituitary‐adrenocortical function in the rat
Authors: HODGES J. R. , MITCHLEY SUSAN 
Published: July 2012

Summary
Both the circadian and stress‐induced changes in plasma corticosterone concentration were abolished by the inclusion of betamethasone in the drinking water of rats.
Adrenal sensitivity to exogenous corticotrophin (ACTH) was unimpaired by the betamethasone treatment.
The normal circadian rhythm in plasma corticosterone returned within 1 day of withdrawal of the steroid, but the response to stress was normal only after 3 days.
The possible significance of these observations is discussed.
The effect of caffeine on the mitosis of human lymphocytes in culture
Authors: TIMSON J. 
Published: July 2012

Summary
The effect of caffeine at concentrations of 10−2m to 10−4<m on the mitotic rate of phytohaemagglutinin‐stimulated human lymphocytes from twelve normal subjects was examined in vitro.
At 10−2m the drug was cytotoxic.
At 10−4m caffeine reduced the rate of mitosis in all cases.
At 10−4m the drug was found to reduce the rate of mitosis in some cases, to give the same value as the control cultures in others and in a third group to increase the mitotic rate.
At 10−4m all the lymphocytes from females showed an increased rate of mitosis and all but one of the lymphocyte samples from males showed a decrease or no change. Thus at this concentration the effect of the drug on the mitotic rate appeared to be related to the sex of the lymphocyte donor. There was also a significant difference in the degree of inhibition between male and female lymphocytes at 10−3m.
Effect of organic nitrates on myocardial oxygen consumption in vitro
Authors: LEVY J. V. 
Published: July 2012

Summary
Mannitol hexanitrate (MANHN), iditol hexanitrate and sorbitan tetranitrate, all at 442 μm, stimulate oxygen uptake by isolated rabbit atrial tissue.
At the same concentration, glyceryl trinitrate decreased oxygen uptake, while isosorbide dinitrate and erythrityl tetranitrate had no effect.
No simple correlation was found between the lipoid solubility or per cent nitration of these compounds and their effects on oxygen uptake.
The stimulating effect of MANHN and its possible role as an uncoupler of oxidative phosphorylation is discussed.
Local anaesthetic and anti‐arrhythmic actions of alprenolol relative to its effect on intracellular potentials and other properties of isolated cardiac muscle
Authors: SINGH B. N. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

SummaryAlprenolol, a β‐adrenoceptor blocking drug reported to have the same potency as propranololin vitroandin vivo, was found to be four times more active than procaine as a local anaesthetic on frog sciatic nerve.At doses of 0·125 mg/kg and above alprenolol protected anaesthetized guinea‐pigs against ouabain‐induced ventricular fibrillation.In isolated rabbit atria, resting potentials were unchanged, and the duration of the action potential was not prolonged, by concentrations of alprenolol up to 10·5 × 10−6m. The maximum rate of depolarization (MRD), however, was reduced by 30% at a concentration of 0·525 × 10−6m. This was 214 times less than the concentration which reduced the frog action potential height by 25%.The concentration of alprenolol required to produce more than 15% decrease in contraction or maximum driven frequency was 3·5 × 10−6m.As a test of the direct action of alprenolol on isolated cardiac muscle, MRD was also a more sensitive test than the measurement of electrical threshold or conduction velocity.
Selective depletion of noradrenaline: a proposed mechanism of the adrenergic neurone‐blocking action of bretylium
Authors: ABBS E. T. , ROBERTSON M. I. 
Published: July 2012

Summary
The effects of bretylium have been investigated on the content and subcellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline in response to stimulation of the splenic nerve.
Bretylium, 15 min after its administration, produces a significant depletion of noradrenaline in only the supernatant fraction of an homogenate; at this time adrenergic neurone blockade is evident. This depletion of noradrenaline is apparent up to 18 h later but has disappeared 7 days after the administration of bretylium when nerve function is also restored.
Both the development of the neurone blockade and the depletion of noradrenaline are prevented by previous administration of (+)‐amphetamine.
In bretylium‐pretreated cats the noradrenaline content of the supernatant fraction is replenished and the neurone blockade is abolished after treatment with (+)‐amphetamine.
The depletion of noradrenaline, which is evident 30 min, 60 min and 18 h after treatment with bretylium, from other subcellular fractions—especially the high‐speed particulate fraction—appears to be unassociated with adrenergic neurone blockade.
It is concluded that bretylium produces its adrenergic neurone‐blocking activity by depleting noradrenaline from a “store” whose amine appears in the supernatant fraction after homogenization. Whilst bretylium is present this “store” cannot refill with noradrenaline.
The antagonism of adrenergic neurone blockade by amphetamine and dexamphetamine in the rat and guinea‐pig
Authors: FOLLENFANT M. J. , ROBSON R. D. 
Published: July 2012

Summary
In isolated rat mesentery preparations, intra‐arterial injection of the following drugs rapidly suppressed vasoconstrictor responses to sympathetic nerve stimulation: bretylium (75–100 μg), guanethidine (10–20 μg) and bethanidine (20–30 μg); with phenoxypropylguanidine (15–30 μg) the onset of blockade was slower. The blockade caused by these or higher concentrations was rapidly abolished by intra‐arterial injection of amphetamine (100 μg) as also was the blockade caused by infusing bretylium or guanethidine for 10–20 min. Partial blockade was produced by 20 μg of reserpine and this was only slightly and briefly antagonized by amphetamine.
In mesentery preparations taken from rats 24 h after subcutaneous injection of bretylium 50 mg/kg, guanethidine 10 mg/kg, phenoxypropylguanidine 10 mg/kg or reserpine 0·1 mg/kg, responses to sympathetic nerve stimulation were greatly impaired. Only in the preparations from the bretylium‐treated rats did amphetamine antagonize the blockade. The adrenergic neurone blocking effect of bethanidine 10 mg/kg was evident at 12 h but not at 24 h after injection.
In rat mesentery amphetamine did not cause vasoconstriction but briefly potentiated the vasoconstrictor effect of sympathetic nerve stimulation. Responses to noradrenaline were not importantly affected.
The contractile responses of the rat inferior eyelid caused by stimulation of the cervical sympathetic nerve was greatly reduced 17–27 h after subcutaneous injection of bretylium 300 mg/kg, bethanidine 30 mg/kg, guanethidine 10 mg/kg or reserpine 0·3 mg/kg. Intravenous dexamphetamine (0·5 mg/kg) powerfully antagonized the effect of bretylium, weakly antagonized the blockade by bethanidine and guanethidine and caused no change in the response of reserpine‐treated animals.
The vas deferens taken from guinea‐pigs 24 h after subcutaneous injection of either bretylium or guanethidine showed greatly impaired responses to hypogastric nerve stimulation. Amphetamine largely restored the contractile response in bretylium‐treated rats but caused only weak antagonism in the guanethidine‐treated animals.
An ultrastructural and histochemical study of the short‐term effects of 6‐hydroxydopamine on adrenergic nerves in the domestic fowl
Authors: BENNETT T. , BURNSTOCK G. , COBB J. L. S. , MALMFORS T. 
Published: July 2012

Summary
The effects of 6‐hydroxydopamine (6‐OHDA) on adrenergic nerves in the domestic fowl have been investigated with ultrastructural and fluorescence histochemical methods.
6‐OHDA depletes the nerves of catecholamine, initially by displacing it from the storage vesicles. 6‐OHDA enters large as well as small vesicles, indicating that large granular vesicles in adrenergic nerves are sites of amine storage.
Doses of 6‐OHDA, insufficient to cause degeneration, still cause loading of the vesicles.
The effects of various drugs on the action of 6‐OHDA indicate that this drug must be taken up by the nerves and reach a critical extragranular axoplasmic concentration before degeneration will occur; 6‐OHDA bound in the vesicles plays no part in the degenerative process.
The effect of amiodarone, a new anti‐anginal drug, on cardiac muscle
Authors: SINGH B. N. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

Summary
Amiodarone (2‐butyl, 3‐(4‐diethylaminoethoxy, 3,5‐diiodo, benzoyl) benzofuran hydrochloride), an anti‐anginal drug which causes coronary dilatation and depresses myocardial oxygen consumption, was found to protect anaesthetized guinea‐pigs against ouabain‐induced ventricular fibrillation.
A 5% (73·4 mm) solution of amiodarone had no local anaesthetic action on guinea‐pig skin.
Amiodarone, 20 mg/kg (29·4 μmol/kg) given daily for 6 weeks intraperitoneally, had no effect on the resting potential or action potential height, and only a small effect on the maximum rate of depolarization, of isolated rabbit atrial or ventricular muscle fibres as shown by intracellular recording. It caused a considerable prolongation of the action potential in both tissues.
Simultaneous administration of thyroxine (5 μg; 6·26 nmol), given daily for 3 weeks intraperitoneally, prevented the prolongation by amiodarone of the duration of the action potential.
Treatment of rabbits with 20 mg/kg of amiodarone daily intraperitoneally for 6 weeks had no effect on the weight of the thyroid gland, but was associated with a reduction in body growth rate.
Treatment of rabbits with 10 mg/kg (60·3 μmol/kg) of potassium iodide (equal in its iodine content to that of 20 mg/kg of amiodarone), given daily for 6 weeks intraperitoneally, had no effect on body growth rate or the duration of cardiac action potentials.
It was concluded that amiodarone had effects on cardiac action potentials similar to those which occur after thyroidectomy.
Noradrenaline and tyramine action on isolated atrial muscle of endotoxin‐treated guinea‐pigs
Authors: BHAGAT B. , CAVANAGH D. , MERRILD B. N. , RANA M. W. , RAO P. S. 
Published: July 2012

Summary
Isolated left‐atrial strips of guinea‐pigs were driven electrically at a constant rate and log‐concentration curves were determined for the positive inotropic effect of noradrenaline and tyramine.
The atrial tissue from endotoxin‐treated animals had a reduced sensitivity to noradrenaline and tyramine.
After endotoxin, the sensitizing effect of cocaine on the response to noradrenaline was normal but accumulation of 3H‐noradrenaline in nerve terminals was markedly reduced.
Atrial tissue of endotoxin‐treated guinea‐pigs responded normally to stretch.
Effects of general depressant drugs on the electrical responses of isolated slabs of cat's cerebral cortex
Authors: FRANK G. B. , JHAMANDAS K. 
Published: July 2012

Summary
In the neuronally isolated cortex of the cat, local application of diphenhydramine, promethazine, gammahydroxybutyrate, gammabutyrolactone, gamma aminobutyric acid, hyoscine and pethidine, and the intravenous injection of diazepam and meprobamate depressed or abolished the surface negative and surface positive response to direct stimulation and raised the stimulus threshold of the positive burst response. These effects were the same as previously demonstrated for general and local anaesthetics on the same preparation.
Chlorpromazine produced a similar depression in small concentrations but caused spontaneous activity in higher concentrations.
In contrast to local application, pethidine when given by intravenous injection in a high dose produced convulsant activity in the isolated cortical slab. The possibility was suggested that the convulsant activity was produced by a metabolite of pethidine.
The results of this investigation suggest that the central depression produced by a number of structurally unrelated drugs is indicative of an anaesthetic‐like property of these drugs.
The effects of histamine in malaria
Authors: MAEGRAITH B. G. , ONABANJO A. O. 
Published: July 2012

Summary
Extracts of the blood of monkeys (Macaca mulatta) infected with Plasmodium knowlesi contain histamine. A mean total concentration of 0·15 μg/ml was present in the circulating blood.
No histamine was detected in the blood of healthy monkeys.
Vasodilatation and increased vascular permeability was observed at the site of injection of the extract into the skin and brain of guinea‐pigs.
Infiltration of the dermal layer by leucocytes was observed after intradermal injection of the histamine extract. A similar response was obtained in the brain.
The extract of the blood from the infected animal produced hypotension in rabbits when administered intravenously.
The pathophysiological significance of histamine in malaria is discussed.
Uptake, metabolism and release of [3H]‐adrenaline by human platelets
Authors: BORN G. V. R. , SMITH J. B. 
Published: July 2012

Summary
Measurements were made of the uptake, metabolism and release of [3H]‐adrenaline by human platelets in citrated plasma or in an artificial medium.
Radioactive adrenaline was not taken up at 0–2° C. At 37° C there was a slow uptake which continued for at least 5 hours.
About half of the radioactivity in the platelets was intact adrenaline. The other half was an acidic metabolite from which adrenaline was released by acid hydrolysis.
The immediate uptake of adrenaline was proportional to its concentration in the plasma up to at least 1 × 10−5m. Uptake measured after 1 h also increased linearly with concentration up to about 1 × 10−4m but less with higher concentrations. The highest concentration ratio was about 12.
The concentration of metabolite in the platelets increased with the concentration of added adrenaline only up to about 2 × 10−4m.
The immediate uptake of adrenaline was partially inhibited by phentolamine and dihydroergotamine. Measurement of uptake both immediately and after 1 h showed that the inhibition produced was not increased beyond about 50% by these drugs or by (±)‐propranolol, chlorpromazine or amitriptyline up to 1 × 10−4m.
Formation of the metabolite was inhibited by pyrogallol, 8‐hydroxyquinoline, or tropolone. This inhibition was associated with a corresponding increase in the adrenaline accumulated intact. Formation of the metabolite was not inhibited by monoamine oxidase inhibitors.
Reserpine caused a small decrease in the uptake of adrenaline radioactivity in 1 h and a great increase in the proportion recovered as metabolite.
Thrombin caused the release from platelets of intact adrenaline but not of the metabolite.
Platelets of albino patients with spontaneous haemorrhages accumulated adrenaline radioactivity at the normal rate but this radioactivity was wholly accounted for by metabolite and not released by thrombin.
After taking up adrenaline, platelets resuspended in artificial medium at 37° C slowly released both adrenaline and its metabolite. At the same time, the intracellular adrenaline was slowly metabolized.
The results suggest that human platelets take up adrenaline by two processes, one of which is inhibited by both α‐ and β‐adrenoceptor blocking agents as well as by phenothiazines; and that in the platelets adrenaline is partly stored in organelles from which, like 5‐hydroxytryptamine, it can be specifically released.
Adrenoceptors of the chick rectum
Authors: BARTLET A. L. , HASSAN T. 
Published: July 2012

Summary
The aim of the investigation was to determine whether the adrenoceptors of the chick rectum preparation complied with Ahlquist's classification; phentolamine (0·1 μg/ml) and propranolol (0·05 μg/ml) were used as specific antagonists of α‐ and β‐adrenoceptors, respectively.
Propranolol antagonized phenylephrine, isoprenaline and noradrenaline in the chick rectum preparation, although according to Ahlquist's classification phenylephrine stimulates α‐adrenoceptors selectively.
In the presence of propranolol, phenylephrine and noradrenaline produced small residual relaxations of the chick rectum preparation which were blocked by phentolamine. In the absence of propranolol, however, phentolamine did not antagonize relaxations to phenylephrine, isoprenaline or noradrenaline.
The adrenoceptors of the guinea‐pig colon preparation compiled with Ahlquist's classification in that they were like those generally present in intestine.
The protective actions of some anticholinergic drugs in sarin poisoning
Authors: BRIMBLECOMBE R. W. , GREEN D. M. , STRATTON JUNE A. , THOMPSON PAMELA B. J. 
Published: July 2012

Summary
The central and peripheral anticholinergic activities of a series of drugs comprising atropine, hyoscine, caramiphen and one of its analogues, and three glycollic acid esters, have been measured.
The ability of the same drugs used alone, and in conjunction with N‐methyl pyridinium‐2‐aldoxime methanesulphonate (P2S), to protect mice, rats and guinea‐pigs from the lethal effects of sarin has been assessed.
No correlation was found to exist between central or peripheral anticholinergic activity and ability to protect from sarin.
On the indirectly stimulated isolated rat phrenic nerve‐diaphragm preparation all drugs with the exception of hyoscine caused potentiation of responses to low frequency stimulation but partial block of responses to high frequency stimulation. The drugs did not reverse the effects of sarin on the phrenic nerve‐diaphragm preparation.
It is concluded that a pharmacological action other than an anticholinergic one is involved, in part, in the protective actions against sarin of some of the drugs studied. Whether their effects on skeletal muscle are of any relevance in this respect is unresolved.
Iontophoretic release of acetylcholine, noradrenaline, 5‐hydroxytryptamine and d‐lysergic acid diethylamide from micropipettes
Authors: BRADLEY P. B. , CANDY J. M. 
Published: July 2012

Summary
The in vitro iontophoretic release of tritium‐labelled acetylcholine and 5‐hydroxytryptamine from large and small micropipettes and noradrenaline and d‐lysergic acid diethylamide from small micropipettes was determined by liquid scintillation counting.
The release was directly proportional to the electrical charge passed in the range normally used in the iontophoretic study of these compounds. The transport numbers obtained for the large micropipettes were approximately double those with the small micropipettes. A very low transport number was found for d‐lysergic acid diethylamide.
The spontaneous leakage was small and did not vary appreciably with time.
The iontophoretic release of acetylcholine in vitro agreed with the in vitro measurements.
The brain‐stem tissue concentration of d‐lysergic acid diethylamide after intravenous injection into intact and decerebrate cats was determined.