bluuebunny/crossref_metadata_2025 huggingface dataset:
Central effects of picrotoxin when acting from the liquor spaces in anaesthetized cats
Authors: FELDBERG W. , GEORGIEV V. P.
Published: July 2012

. Picrotoxin was perfused through different parts of the cerebral ventricles in cats anaesthetized with chloralose, and applied topically to the upper cervical cord in cats anaesthetized with intraperitoneal pentobarbitone sodium. With both methods, picrotoxin produced effects similar to those produced by tubocurarine; but it was active in weaker concentrations.

. Perfused through the third ventricle, picrotoxin caused shivering resulting in a rise of rectal temperature, increased motor excitability, muscle jerks, tachypnoea, mydriasis, and withdrawal of the nictitating membranes. The effects were due to an action on structures in the walls of the ventral half of the ventricle, because they occurred only on perfusion of tubocurarine through this half and not on its perfusion through the dorsal half of the third ventricle. Noradrenaline perfused through the third ventricle abolished the shivering and the rise in temperature, but did not affect the motor hyperexcitability or the muscle jerks, whereas pentobarbitone sodium similarly perfused abolished these effects as well.

. Perfused through the inferior horn of a lateral ventricle, picrotoxin caused excitation of the hippocampus. This resulted in a rhythmic discharge of high voltage negative spikes in the electrocorticogram taken from the occipital cortices. The spikes developed after‐positivity with after‐discharges and were interrupted from time to time by bursts of fast activity termed episodes. This abnormal discharge was recorded also from the perfusion cannula which was inserted into the inferior horn and acted as a lead from the surface of the hippocampus.

. Perfused through the anterior horn of a lateral ventricle picrotoxin caused a rhythmic discharge of negative spikes which was recorded from the anterior horn cannula and resulted from excitation of the grey matter in the anterior limbic area which forms part of the medial wall of the horn.

. Applied to the surface of the upper cervical cord, picrotoxin produced scratching movements.
An analysis of the coronary vascular responses to catecholamines, using a modified Langendorff heart preparation
Authors: BROADLEY K. J.
Published: July 2012

. A modified Langendorff heart preparation from the guinea‐pig was used to analyse catecholamine responses. Contractile force, heart rate and coronary perfusion pressure were recorded.

. Four components of the vascular response could be identified.

The initial phase was a vasoconstriction mediated by α‐adrenoceptors which preceded any effects on heart rate and force.

A secondary constriction followed, which was due to the increased myocardial compression during positive inotropic and chronotropic responses.

The third, more predominant, effect was a prolonged dilatation probably associated with the increased metabolic activity of the heart.

A fourth component was a direct vasodilatation mediated by β‐adrenoceptors which was evident when small doses of catecholamines were used but was usually masked by the more pronounced metabolically linked dilatation.

. The actions of salbutamol were examined and since it caused direct vasodilatation by stimulation of β‐adrenoceptors without other myocardial effects, these adrenoceptors were classified as the β2‐type.

. I.C.I. 50,172 was employed to block selectively the myocardial effects due to stimulation of β1‐adrenoceptors and leave the vasodilator β2‐adrenoceptors unaffected.

. Adrenaline, noradrenaline and isoprenaline were compared at two dose levels, in the presence or absence of effects on heart rate and force.

. Constrictor or dilator effects were found in the absence of other effects and were shown to depend to some extent on the rate of coronary perfusion.
Effects of catecholamines infused into the brain of young chickens
Authors: MARLEY E. , STEPHENSON J. D.
Published: July 2012

. (–)‐Noradrenaline, (–)‐α‐methylnoradrenaline and (–)‐isoprenaline were infused into various brain regions of 12–21 day chicks. When infused into the hypothalamic area, but not the cerebral hemisphere or posterior mesencephalon, these amines produced behavioural sleep, lowered temperature and blood pressure and reduced oxygen consumption; electrocortical sleep activity usually ensued but this was not marked and frequently dissociation between electrocortical activity and behaviour occurred. After monoamine oxidase inhibition, which prolonged the action of noradrenaline, dopamine had similar effects.

. The effects of the catecholamines were prevented or substantially reduced by pretreatment with phenoxybenzamine given intravenously or into the hypothalamus but not by intravenous injection of propranolol. However, intrahypothalamic infusion of propranolol prevented the temperature, but not the behavioural effects of noradrenaline. The implications of this are discussed.

. That the effects were similar but more intense, apart from electrocortical changes, and of longer duration than those seen after intravenous injection of catecholamines suggests that in young chicks these amines penetrate from the blood into the brain and elicit their effects through a localized region, presumably the hypothalamus.
An investigation of α‐methyl amino‐acids and their derivatives on isolated tissue preparations
Authors: GULATI O. D. , PARIKH H. M. , RINGE S. Y. , SHERLEKAR M. L.
Published: July 2012

. The ability of α‐methyl amino‐acids and their corresponding amines to restore the sympathomimetic actions of tyramine, and the uptake of the amino‐acids and the amines, were studied in isolated tissue preparations obtained from reserpine pretreated animals.

. Tyramine relaxed isolated rat ileum preparations from non‐reserpinized rats but not from reserpine treated animals. α‐Methyldopa, α‐methylnoradrenaline and lower concentrations of metaraminol restored the responses of reserpinized preparations. α‐Methyldopamine, α‐methyl‐m‐tyrosine, α‐methyl‐p‐tyrosine and higher concentrations of metaraminol did not do so. The restoring effect of α‐methyldopa was blocked by disulphiram. α‐Methyl‐p‐tyrosine or α‐methyl‐m‐tyrosine blocked the restoring action of α‐methyldopa but not of α‐methylnoradrenaline. Cocaine blocked the restoration of responses to tyramine by α‐methylnoradrenaline but not by α‐methyldopa. α‐Methyldopa and α‐methylnoradrenaline failed to restore responses to tyramine in the presence of sodium‐free Tyrode solution.

. Tyramine increased the perfusion pressure in isolated rabbit ear preparations obtained from non‐reserpinized animals but was very much less active in preparations obtained from reserpine treated animals. α‐Methyldopa, α‐methyl‐m‐tyrosine, α‐methylnoradrenaline, α‐methyl‐p‐tyrosine and metaraminol restored the effects of tyramine. α‐Methyldopamine did not do so. The restoring effect of α‐methyldopa and α‐methyl‐m‐tyrosine was blocked by disulfiram. α‐Methyl‐p‐tyrosine blocked the restoring effect of α‐methyl‐m‐tyrosine.

. Tyramine produced positive inotropic effects in isolated rabbit heart preparations. This was either reduced or absent in preparations obtained from reserpine pretreated animals. α‐Methyldopa, α‐methylnoradrenaline, α‐methyl‐m‐tyrosine and metaraminol restored the responses to tyramine. α‐Methyldopamine and α‐methyl‐p‐tyrosine did not do so.
Effect of caerulein on protein synthesis and secretion in the guinea‐pig pancreas
Authors: MELDOLESI J.
Published: July 2012

. Caerulein produced a striking increase in the rate of secretion of the guinea‐pig pancreas. When tested in vivo with pancreatic slices its optimal concentration was found to be 2.5 ng/ml. In vivo the intravenous injection of 400 ng/kg and the subcutaneous injection of 4 μg/kg of the drug produced marked secretory responses.

. Neither incubation of pancreatic slices in vitro for various lengths of time in the presence of caerulein nor the intravenous injection of the drug brought about any detectable changes in the rate of 14C‐l‐leucine incorporation into protein of pancreatic slices incubated in vitro. By contrast, a two‐fold increase in the incorporation of leucine was found in fasting animals injected subcutaneously with caerulein twice a day for 4 days. The same treatment in fed animals, or one single dose of caerulein injected subcutaneously 4 h before killing in guinea‐pigs starved for 4 days did not affect the rate of incorporation. Moreover the long term treatment with the cholinergic segretagogue bethanechol in fasted guinea‐pigs was also ineffective.

. It is concluded (a) that in the guinea‐pig pancreas, stimulation of enzyme secretion does not affect per se the rate of synthesis of digestive enzymes; and (b) that the increase of protein synthesis elicited by caerulein is critically dependent both on the nature of the segretagogue (that is, it is elicited by the polypeptide but not by a cholinergic drug) and on the experimental conditions (it is evident only in fasted animals after prolonged treatment).
Recovery of hypothalamo‐pituitary‐adrenal function in the rat after prolonged treatment with betamethasone
Authors: HODGES J. R. , MITCHLEY SUSAN
Published: July 2012

. Betamethasone caused growth retardation, adrenal atrophy and impaired hypothalamo‐pituitary‐adrenal (HPA) activity in the rat.

. In spite of the profound impairment, recovery of normal HPA function was rapid, but the growth retardation persisted.

. The ability of the pituitary gland to secrete basal corticotrophin (ACTH), recovered more rapidly and the adrenocorticotrophic response to stress less rapidly than the ability of the adrenal cortex to respond to ACTH.

. The degree of HPA suppression was not determined by the total dose of steroid.

. The possible significance of the results is discussed.
The effect of thyroid hormones on the action of some centrally acting drugs
Authors: COVILLE P. F. , TELFORD J. M.
Published: July 2012

. The effect of administration of thyroxine or thyroidectomy on the pharmacological action of (+)‐amphetamine, caffeine, hexobarbitone and morphine was determined in rats or mice.

. Locomotor activity induced by (+)‐amphetamine or caffeine was increased by hyperthyroidism and decreased by hypothyroidism.

. The LD50s of (+)‐amphetamine and caffeine in hyperthyroid rats were 1/30 and 2/5 that of control rats. With each drug, the LD50 regression lines in hyperthyroid and control rats were not parallel, suggesting that hyperthyroidism modifies the mechanism of the toxic effects. Hypothyroidism reduced toxicity to (+)‐amphetamine.

. Hexobarbitone sleeping time was prolonged in hyperthyroid male rats, but was shortened in hyperthyroid female rats. In control rats, sleeping time was approximately four times as long in females as it was in males. Ethinyloestradiol treatment and castration also prolonged sleeping time in male rats. No further prolongation was produced by combined administration of thyroxine and ethinyloestradiol, but thyroxine further prolonged the sleeping time of castrated rats indicating that its mode of action in producing these changes is not mediated via sex hormones.

. In contrast to rats, a sex difference in the duration of action of hexobarbitone was not found in mice. Thyroxine prolonged sleeping time equally in each sex.

. Analgesia induced by morphine in mice was unaffected by hyperthyroidism. No increase in sedative or ‘Straub tail’ activity could be detected, but toxicity was increased when higher doses of morphine were used.

. The mechanism by which thyroid hormones produce these changes in sensitivity to centrally acting drugs is discussed. It is suggested that the effects of thyroxine vary according to whether the mode of action of the drug or its metabolism is modified.
Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit
Authors: KENDLE K. E. , TELFORD J. M.
Published: July 2012

. Experiments have been performed to investigate the mechanism by which low doses of megestrol acetate have an antifertility action.

. It was found that the dose of megestrol acetate required to prevent pregnancy in nine of ten New Zealand White rabbits when given on 3 consecutive days, the last of which was the day of insemination, was 50 μg/kg daily.

. This treatment reduced the numbers of sperm recoverable from the uterus at various times after insemination, but egg transfer experiments showed that neither egg viability nor fertilization was affected on day 1 of pregnancy.

. Treatment with megestrol acetate for 3 days caused the fertilized eggs to enter the uterus approximately 48 h prematurely. Treatment with megestrol acetate for longer periods caused a similar but more marked increase in the rate of transport of eggs in the oviduct.

. Megestrol acetate did not modify oviduct opening pressure, but the volume of oviduct fluid secretion was reduced earlier and transport of fluid through the oviduct was accelerated compared with controls.

. Transfer of eggs on various days from the uteri of untreated rabbits to the uteri of treated rabbits indicated that the development of the endometrium which occurs in pregnancy may be advanced by megestrol administration. Histological examination of the endometrial proliferation induced by megestrol acetate confirmed that this was so.

. It is concluded that the antifertility action of megestrol acetate in doses that do not necessarily inhibit ovulation is due to a combination of accelerated egg transport and advanced endometrial development.
Time course of the effects of 6‐hydroxydopamine on catecholamine‐containing neurones in rat hypothalamus and striatum
Authors: BELL LINDA J. , IVERSEN L. L. , URETSKY N. J.
Published: July 2012

. The effects of intraventricular injection of 6‐hydroxydopamine (6‐OHDA) on tyrosine hydroxylase activity, uptake of 3H‐noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6‐OHDA.

. In the hypothalamus after the injection of 250 μg of 6‐OHDA there was a rapid decrease in tyrosine hydroxylase activity, 3H‐noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours.

. In the striatum after this dose of 6‐OHDA there was a much slower reduction in tyrosine hydroxylase activity and 3H‐noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.

. After the injection of a smaller dose of 6‐OHDA (25 μg) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity.

. These results are consistent with the hypothesis that 6‐OHDA causes a rapid degeneration of catecholamine‐containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6‐OHDA, except possibly at early times after the administration of small doses of the drug.
Uptake of monoamines into central neurones and the blood‐brain barrier in the infant rat
Authors: LOIZOU L. A.
Published: July 2012

. A fluorescence histochemical study was undertaken to investigate the ability of systemically administered monoamines to penetrate into the central nervous system of infant rats.

. It was found that after subcutaneous injections of large doses, l‐noradrenaline, l‐α‐methyl‐noradrenaline, dl‐α‐methyl‐dopamine, l‐α‐methyl‐dopa and 5‐hydroxytryptamine could cross the blood‐brain barrier of newborn to 2 week old rats and be taken up by neurones normally containing monoamine as well as by several neurones which normally contained no monoamine.

. 5‐Hydroxytryptamine containing neurones took up 5‐hydroxytryptamine as well as catecholamines and α‐methyl‐dopa. The pinealocytes, which contain large amounts of 5‐hydroxytryptamine, were depleted of their endogenous fluorescence by α‐methyl‐dopa and showed no selective uptake of catecholamines.

. The uptake of monoamines was not antagonized by previous reserpine treatment or by inhibition of catecholamine synthesis, and occurred throughout the whole extent of the monoamine‐containing neurones (cell body, axon, terminals).

. The monoamines were also taken up by the endothelial cells and pericytes of capillaries in the central nervous system (CNS) which are thought to constitute the physical barrier to these substances in the adult.

. The peripheral sympathetic nerves to pial blood vessels, the pineal and pituitary glands also took up the monoamines and α‐methyl‐dopa; uptake was also noted in cells of the pituitary gland, in epithelial and connective tissue elements of the meninges and choroid plexuses and in the epithelial, connective and muscular tissue of pial blood vessels.

. It is concluded that the blood‐brain barrier to monoamines may not be fully developed in infant rats, at least for high levels of circulating monoamines; the central monoamine‐containing neurones possess the ‘membrane pump’ mechanism for uptake of monoamines from the time of birth, even though they are not fully developed morphologically.
Effects of sulphydryl inhibitors on frog sartorius muscle: p‐chloromercuribenzoic acid and p‐chloromercuribenzenesulphonic acid
Authors: KIRSTEN E. B. , KUPERMAN A. S.
Published: July 2012

. Experiments were done on frog sartorius muscles to study the effects and mechanisms of action of the –SH inhibitors, p‐chloromercuribenzoic acid (PCMB) and p‐chloromercuribenzenesulphonic acid (PCMBS).

. Both organomercurials produce a depolarization of the surface membrane which is associated with a period of asynchronous twitching and followed by inexcitability.

. Only PCMB produces a unique fractionation of the electrically evoked twitch into an initial rapid and later slow phase.

. PCMB and PCMBS increase the rate of 45Ca efflux from whole muscle. Ethylenediamine tetraacetic acid (EDTA, 5 mm) causes only limited antagonism of the enhancement of 45Ca efflux produced by PCMB whereas it completely antagonizes this same effect of PCMBS. EDTA selectively removes superficial calcium without penetrating into the intracellular space.

. The results suggest that PCMB inhibits –SH groups in the terminal cisternae causing a fractionation of the twitch. PCMBS acts primarily at surface sites with limited access to the cisternae and sarcoplasmic reticulum.
Effects of sulphydryl inhibitors on frog sartorius muscle: N‐ethylmaleimide
Authors: KIRSTEN E. B. , KUPERMAN† A. S.
Published: July 2012

. The characteristic action of the –SH inhibitor, N‐ethylmaleimide (NEM), is muscle rigour. The dose‐response curve indicates a biphasic effect with maximum rigour tension produced by 10 mm NEM; beyond 1.0 mm there was an inverse relationship between dose and response.

. NEM produces a membrane depolarization unrelated to rigour development.

. NEM causes a sustained increase in 45Ca efflux from whole muscle. Pretreatment of a muscle with ethylenediamine tetra‐acetic acid (EDTA, 5 mm) to remove membrane calcium does not alter the NEM induced 45Ca efflux.

. It is suggested that the primary site of NEM action is inhibition of calcium uptake by the sarcoplasmic reticulum thereby producing rigour. At concentrations above 1.0 mm, NEM may affect the myofilaments.
Two toxins from a poisonous sample of mussels Mytilus edulis
Authors: EVANS M. H.
Published: July 2012

. A crude preparation of toxin was extracted from a sample of mussels Mytilus edulis, part of a batch responsible for many cases of paralytic shellfish poisoning.

. The crude extract was partially purified by absorption on sodium Amberlite ion‐exchange resin. Two toxins were recovered by elution from the Amberlite, and purified further by gel filtration.

. One toxin closely resembled saxitoxin in its behaviour on Amberlite and in its biological effects.

. The other toxin behaved quite differently on the Amberlite. Its molecule was small, comparable in size with saxitoxin. It was not tetrodotoxin. Its biological effects were similar, but not identical, to those of saxitoxin: it paralysed muscular contraction and inhibited conduction along nerves; it caused death of experimental animals by producing a peripheral paralysis of respiration; it did not depolarize the membrane of frog skeletal muscle fibres, but acted by preventing a stimulus from initiating a conducted action potential.

. The biological effects of the second toxin suggest that, like saxitoxin and tetrodotoxin, it is an inhibitor of inward sodium ion movement through electrically excitable membranes.
Effects of stress and betamethasone on the production of corticosterone by the rat adrenal gland in vitro
Authors: HODGES J. R. , MITCHLEY SUSAN
Published: July 2012

Production of corticosterone in vitro was studied using adrenal glands from rats which had been subjected to stress or treated with betamethasone.

An increase in corticosterone production occurred in the first but not the second hour of incubation in adrenals removed immediately after stress. When the interval between stress and adrenalectomy was longer, the increased corticosterone production persisted.

Betamethasone had no effect on corticosteroidogenesis in vitro when added directly to the incubation medium or when administered to rats shortly before removal of their adrenal glands.

Corticosteroidogenesis in vitro was considerably reduced in the adrenals of rats given prolonged treatment with betamethasone.

The significance of the results and the reliability of in vitro corticosteroid production as an index of hypothalamo‐pituitary‐adrenal activity is discussed.
Effect of tetrabenazine and α‐methyl‐m‐tyrosine on exploratory activity and brain catecholamines in rats
Authors: ONN‐LENG CHAN , WEBSTER R. A.
Published: July 2012

Spontaneous exploratory locomotor activity of Wistar rats was measured in photocell activity cages, and brain noradrenaline (NA) and dopamine (DA) were determined fluorometrically after ion exchange purification.

Tetrabenazine (TBZ) (10 mg/kg) produced a fall in NA and DA concentrations in rat brain stems which was correlated with the fall in activity in female Wistar rats.

α‐Methyl‐m‐tyrosine (αMMT) reduced the concentration of rat brain NA without affecting DA concentration or activity.

Pretreatment with αMMT did not stop TBZ from producing a marked reduction in activity and NA concentration, but partially protected DA from the depleting action of TBZ.

These results support a role for catecholamines in the control of motor activity, but they do not implicate NA more than DA and they emphasize that the mechanism by which drugs affect the concentrations of catecholamines may be more important than the gross concentrations attained.
Cardiovascular effects of morphine, pethidine, diamorphine and nalorphine on the cat and rabbit
Authors: GRUNDY H. F.
Published: July 2012

The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although, occasionally, a pressor action may predominate or intervene.

Possible mechanisms of the depressor phases of action have been studied on cardiac and vascular preparations both in situ and in vitro.

While in the whole animal, catecholamine release from the adrenal medulla and histamine liberation may be implicated in the responses, the vasodilator and vascular relaxant actions of morphine and, probably, pethidine, nalorphine and diamorphine on the isolated preparations are not mediated by the liberation of known peripheral transmitters or autacoids or by interaction with their specific receptors.
Inhibition by atropine of the increased turnover of noradrenaline in the hypothalamus of rats exposed to cold
Authors: SIMMONDS M. A.
Published: July 2012

Small doses of (—)‐[3H] noradrenaline were injected into the lateral cerebral ventricles in rats to label radioactively the endogenous noradrenaline (NA) stores.

Intraventricular injection of 25 μg atropine methonitrate at the same time inhibited the increased rate of disappearance of [3H] NA from the hypothalamus at an environmental temperature of 9° C, when compared with the values at 24° C, without impairing temperature regulation.

At 32° C, 25 μg atropine methonitrate caused a lethal hyperthermia. A dose of 5 μg was not lethal and did not inhibit the increased rate of disappearance of [3H] NA from the hypothalamus.

It is concluded that the pathway which stimulates an increased turnover of NA in the cold contains an atropine sensitive synapse but is not the principal pathway of heat production. The increased turnover of NA in the heat probably does not involve an atropine sensitive synapse.
Effect of frequency of stimulation on the inhibition by noradrenaline of the acetylcholine output from parasympathetic nerve terminals
Authors: KNOLL J. , VIZI E. S.
Published: July 2012

The relationship between the number of shocks delivered, the frequency of stimulation and the acetylcholine output per volley from nerve terminals of the longitudinal muscle strip of the guinea‐pig ileum was studied.

There was an inverse correlation between acetylcholine output per volley and the frequency of stimulation when the same number of shocks was applied in each train.

With sustained stimulation, the volley output declined more rapidly the higher the frequency of stimulation. There was no decrease in volley output (11·7 (ng/g)/volley) when the frequency applied was 0·1 Hz or less.

Noradrenaline (10−6 g/ml) reduced the acetylcholine output per volley to the level produced by sustained stimulation at 10 Hz (1·4–1·9 (ng/g)/volley). The acetylcholine output following application of the first shocks of a train at high frequency stimulation was much reduced by noradrenaline as the output was higher than 1·4–1·9 (ng/g)/volley. This action of noradrenaline was antagonized by phentolamine (2 μg/ml for 20 min).

Amphetamine and methylamphetamine, which release NA from sympathetic nerve terminals, were active in reducing the acetylcholine output to low frequency parasympathetic nerve stimulation. Reserpine and α‐methyl‐p‐tyrosine pretreatment prevented the effect of amphetamine and reduced that of methylamphetamine.

The fact that addition or release of noradrenaline, reduced acetylcholine output when the firing rate was high but short in duration, suggests that noradrenaline plays a general modulator role in controlling the output of acetylcholine from the parasympathetic nerve terminals.
Excitation of certain posterolateral hypothalamic units by cyclopropane and ether
Authors: MILLAR R. A. , SILVER I. A.
Published: July 2012

Extracellular activity was recorded from single units in the posterolateral hypothalamus in nineteen cats before, during, and after the administration of the inhalation anaesthetics cyclopropane, diethyl ether and halothane.

Unit discharge was significantly increased by 25–50% cyclopropane in eighteen of the forty‐four cells tested with this anaesthetic, and in seven of fourteen cells tested with diethyl ether. This excitatory effect was associated with cortical EEG suppression.

The remaining cells tested were depressed by cyclopropane or ether, and this also occurred during halothane administration.

Excitation of certain cells in the posterolateral hypothalamus is discussed in relation to the increased preganglionic sympathetic activity evoked by cyclopropane and ether.
Factors affecting the action of guanethidine on adrenergic neurones
Authors: GULATI O. D. , JAYKAR SAROJA
Published: July 2012

The uptake of guanethidine by adrenergic neurones has been studied indirectly by testing the ability of various procedures to prevent or reverse adrenergic neurone blockade in the periarterially stimulated isolated ileum preparation.

Adrenergic neurone blockade was prevented but not reversed by equilibration with guanethidine (3·3 × 10−6m) at low temperatures (10° C), in the absence of sodium or in the presence of tetrodotoxin (0·3 × 10−6m) or noradrenaline (1·2 × 10−3m).

Calcium (5 × 10−2m) both prevented and, to some extent, reversed the adrenergic neurone blocking action of guanethidine.

Equilibration with guanethidine in the presence of mersalyl (0·6 × 10−7m) or in the absence of potassium or calcium could neither prevent nor reverse adrenergic neurone blockade.
Release of dopamine from bovine lung by specific antigen and by compound 48/80
Authors: EYRE P. , DELINE T. R.
Published: July 2012

Dopamine was shown to be released from the isolated lung of calves sensitized with horse serum by compound 48/80 and by specific antigen.

Dopamine contracts the bovine pulmonary artery and pulmonary vein. Phentolamine, the α‐adrenoceptor blocking agent, inhibits this activity of dopamine and also strongly reduces the Schultz‐Dale response of the pulmonary vessels.

The results are consistent with the suggestion that dopamine (together with histamine and 5‐hydroxytryptamine) may participate in the pulmonary vasoconstriction associated with anaphylaxis in cattle.
Effects of α‐methyl‐p‐tyrosine, p‐chlorophenylalanine, l‐β‐(3,4‐dihydroxyphenyl)alanine, 5‐hydroxytryptophan and diethyldithiocarbamate on the analgesic activity of morphine and methylamphetamine in the mouse
Authors: MAJOR C. T. , PLEUVRY BARBARA J.
Published: July 2012

The analgesic activity of sympathomimetic drugs does not appear to involve a peripheral component.

Drugs causing changes in morphine analgesia have similar effects on the analgesia produced by methylamphetamine.

The analgesia produced by morphine and methylamphetamine is increased by drugs which increase the ratio of brain 5‐hydroxytryptamine (5‐HT) to dopamine.

The analgesia is decreased by drugs causing a fall in brain 5‐HT or a rise in dopamine relative to 5‐HT.
Action of 6‐hydroxydopamine on lamb sympathetic ganglia, vas deferens and adrenal medulla: a combined histochemical, ultrastructural and biochemical comparison with the effects of reserpine
Authors: CHEAH T. B. , GEFFEN L. B. , JARROTT B. , OSTBERG A.
Published: July 2012

The effects of a single dose of 6‐hydroxydopamine (6‐OHDA) compared with those of chronic reserpine treatment were studied in lamb sympathetic neurones and adrenal medulla by a combination of fluorescence histochemistry, electron microscopy and radiochemical assay.

In sympathetic ganglia, 6‐OHDA produced a rise in noradrenaline concentration within 24 h, and falls in tyrosine hydroxylase and monoamine oxidase activities, whereas reserpine caused a fall in noradrenaline, a rise in tyrosine hydroxylase activity and no change in monoamine oxidase activity. The fluorescence of intra‐ and postganglionic axons increased greatly within 24 h of 6‐OHDA, and there was a corresponding accumulation of large dense‐core vesicles within many axons whose neurotubules were disrupted. The changes were almost reversed after 3 weeks.

In the vas deferens, the concentration of noradrenaline and tyrosine hydroxylase and monoamine oxidase activities had all fallen 24 h after 6‐OHDA treatment and had started to recover 3 weeks later. In the adrenal medulla, 6‐OHDA did not alter NA concentrations but increased tyrosine hydroxylase activity whereas reserpine depleted noradrenaline and increased tyrosine hydroxylase activity.

The changes produced in sympathetic ganglia by 6‐OHDA may be due both to a direct action on the axoplasmic transport of noradrenaline containing vesicles and indirectly to the reaction of the neurones to loss of the integrity of their axons.
Inhibitory effects of aprotinin on kallikrein and kininases in dog's blood
Authors: POJDA S. M. , VANE J. R.
Published: July 2012

The blood‐bathed organ technique was used in dogs to estimate kinin generation in the blood. Strips of cat jejunum were used as assay tissues.

Infusions of kallikrein at 0·5–8 mu/ml into the blood in the extracorporeal circuit led to a generation of kinin at 0·6–10 ng/ml. The kinin generated was at the same concentration after incubation of kallikrein with blood for 15 s or 120 seconds. Intravenous infusions of kallikrein at (8–125 mu/kg)/min led to similar blood concentrations of kinin. These infusions induced substantial falls in blood pressure.

Aprotinin inhibited the generation of kinin by kallikrein, but the concentration needed in vivo was 20,000 times higher than would be expected from the definition of the units.

After intravenous injection of large doses of aprotinin, the kallikrein‐inhibiting activity passed off within 40–60 minutes. At the same time, there was a gradual reduction in kininase activity, so that the half life of bradykinin in blood increased from a mean of 13 s to 40 seconds. This effect reached a maximum 1–3 h after injection of aprotinin.

It is suggested that a metabolite of aprotinin is responsible for the kininase inhibition and that this effect may limit the usefulness of aprotinin in man.
Identification of prostaglandins in prevertebral venous blood after preganglionic stimulation of the cat superior cervical ganglion
Authors: DAVIS HEATHER A. , HORTON E. W. , JONES K. B. , QUILLIAM J. P.
Published: July 2012

In four out of seven experiments, prostaglandin‐like activity was detected in prevertebral venous blood from the superior cervical ganglion, collected during and after preganglionic nerve stimulation.

Prostaglandins E1, E2, F2α and a prostaglandin A were identified using solvent partition, column and thin‐layer chromatography and bioassay techniques.

The release of PGF2α was confirmed by combined gas chromatography‐mass spectrometry.
Suppression of adrenocorticotrophic activity in the ascorbic acid deficient guinea‐pig
Authors: HODGES J. R. , HOTSTON R. T.
Published: July 2012

Adrenocortical hyperactivity caused by a marked increase in circulating corticotrophin occurred in guinea‐pigs on a diet deficient in ascorbic acid.

Betamethasone prevented the rise in the blood ACTH concentration in scorbutic animals and also the increased steroid production per gramme adrenal tissue in vitro. It diminished the adrenal hypertrophy and partially suppressed the rise in plasma Cortisol.

Ninety minutes after the injection of ascorbic acid corticotrophin could no longer be detected in the plasma of scorbutic animals.

Neither the survival time nor the weight loss was affected by betamethasone treatment.
Comparison of the effects of isoprenaline, orciprenaline, salbutamol and isoetharine on the cardiovascular system of anaesthetized dogs
Authors: EKUE J. M. KOFI , SHANKS R. G. , ZAIDI S. A.
Published: July 2012

The intravenous injection of isoprenaline, orciprenaline, salbutamol and isoetharine increased heart rate in anaesthetized dogs. Log dose‐response curves obtained with a series of doses of salbutamol and isoetharine were flatter than those for isoprenaline and orciprenaline. The order of activity of the drugs in increasing heart rate was isoprenaline, orciprenaline, and salbutamol=isoetharine.

The injection into the external iliac artery of isoprenaline, orciprenaline, salbutamol and isoetharine produced dose dependent increases in femoral blood flow. Log dose‐response curves for all drugs were parallel. The order of activity of the drugs was isoprenaline, salbutamol=isoetharine and orciprenaline.

Salbutamol and isoetharine were less active than orciprenaline in increasing heart rate but more active in increasing femoral blood flow.

These observations indicate that salbutamol and isoetharine have a greater effect on β2 than on β1‐adrenoceptors in the cardiovascular system.
Passage into the rat brain of dopa and dopamine injected into the lateral ventricle
Authors: CONSTANTINIDIS J. , GAILLARD J. M. , GEISSBUHLER F. , TISSOT R.
Published: July 2012

The green fluorescence of catechols of the brain was studied in rats after intraventricular injection of l‐dopa or dopamine in untreated rats as well as in rats in which dopa decarboxylase (DC) was inhibited by Ro 4602, or the monoamine oxidase by nialamide.

From the patterns of fluorescence obtained in these conditions, it is concluded that in the areas close to the liquor space dopa is rapidly taken up by the endothelium of the brain capillaries and then converted into dopamine; when the DC is inhibited the dopa passes freely from the endothelium into the brain tissue.

On the other hand, dopamine passes from the liquor space via the ependyma directly into the brain tissue and from there into the capillary endothelium which is thus permeable to the amine in the direction from the brain tissue, in contrast to the impermeability in the direction from the capillary lumen.
Impulse transmission in the myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum
Authors: KOSTERLITZ H. W. , LYDON R. J.
Published: July 2012

In a preparation consisting of the myenteric plexus and the longitudinal muscle layer removed from a segment of guinea‐pig ileum, spontaneous action potentials occurred which were unaffected by tetrodotoxin but suppressed by Mn2+ and were therefore myogenic.

A single current pulse of 0·1 ms duration evoked a response consisting of an early action potential followed after a delay of about 200 ms by a complex of biphasic spikes. The first action potential was conducted for no more than 15 mm and the second complex for 30–70 mm.

Since the first action potential was unaffected by hyoscine or Mn2+ but abolished by tetrodotoxin, it was due to excitation of nerve fibres. The later complex of spikes was suppressed by hyoscine and Mn2+ and therefore due to excitation of smooth muscle. It was also inhibited by adrenaline or morphine, compounds which depress acetylcholine release. The evoked smooth muscle response was followed by absence of spontaneous electrical activity for 2–4 seconds.

The nerves travelling in a longitudinal direction had a mean maximum conduction velocity of 0·65 m/s, an absolute refractory period of 2·8 ms and a relative refractory period of about 20 ms.

The conduction velocity of the smooth muscle response evoked by stimulation of the nerve with a single pulse was 0·16 m/second. After a single pulse the muscle was inexcitable for 0·7–1·3 s; the delay of transmission from nerve to muscle was 210 ms. When instead of a single pulse a train of two—five pulses at 20 ms intervals was applied, the size, conduction distance and conduction velocity of the evoked smooth muscle response were increased.
Release of noradrenaline and dopamine by nerve stimulation in the cat spleen perfused with 3H‐dopamine
Authors: KIRPEKAR S. M. , YAMAMOTO H.
Published: July 2012

Recovery of 3H‐dopamine and 3H‐l‐dopa infused intra‐arterially at a constant rate of 20 ng/min into the cat spleen perfused with Krebs bicarbonate solution was 52·6 ± 3·8% and 90·5 ± 3·1% respectively. Recovery of 3H‐dopamine in spleens treated with α‐methyl‐p‐tyrosine was 67·7 ± 6·7% and was not significantly different from untreated spleens.

Release of 3H‐dopamine by nerve stimulation after an infusion of 3H‐dopamine resembled release of endogenous noradrenaline. Release of 3H‐l‐dopa and 3H‐l‐tyrosine after their infusion did not occur in any consistent manner by nerve stimulation.

Preferential release of 3H‐noradrenaline formed from 3H‐dopamine was not observed during continuous nerve stimulation. Specific activity of released 3H‐noradrenaline remained constant during any single stimulation period with or without 3H‐dopamine infusion. Treating the cats with α‐methyl‐p‐tyrosine did not change the time course of 3H‐noradrenaline release.

Output of noradrenaline expressed as a percentage of the first minute output in both normal and α‐methyl‐p‐tyrosine treated spleens was not significantly different at various times during continuous nerve stimulation.

Specific activity of released noradrenaline formed from 3H‐dopamine was always greater than the specific activity of the spleen in normal spleens and spleens treated with α‐methyl‐p‐tyrosine.

It is concluded that newly synthesized or infused noradrenaline initially mixes with a more rapidly turning pool and only slowly with the entire tissue store. During continuous nerve stimulation there is no further preferential release of newly synthesized noradrenaline. Released noradrenaline truly represents the state of the releasable pool and will vary with the latter.
Excretion of nitrofurantoin in dog hepatic bile
Authors: CONKLIN J. D. , WAGNER D. L.
Published: July 2012

After the intravenous administration of nitrofurantoin sodium to dogs at nitrofurantoin doses of 1·5–24·0 mg/kg, a substantial amount of nitrofurantoin is excreted in bile. The bile to blood drug ratios were about 200. A marked hydrocholeretic effect which correlated directly with the amount of nitrofurantoin administered was also observed.

The excretion of nitrofurantoin in bile and the hydrocholeretic effect were linear with the dose of drug over the range 1·5–12·0 mg/kg. Maximum increases in hepatic bile flows were usually from 5–10 ml/0·5 h, while average control bile flow was 1·6 ml ± s.d. 0·6/0·5 hours. The lowest dose at which the hydrocholeretic effect was still detectable was 0·09 mg/kg.

Apparent saturation of the biliary excretion system for nitrofurantoin and the hydrocholeretic mechanism occurred after a dose of 24·0 mg/kg. Saturation of the urinary system for nitrofurantoin excretion was noted after a dose of 6·0 mg/kg.

Biliary nitrofurantoin recoveries ranged from 16·5% ± s.d. 4·2 to 22·6% ± s.d. 4·7 for the 6 h period after doses of 1·5, 30, and 6·0 mg/kg. Urinary nitrofurantoin recoveries for the same interval ranged from 24·1% ± s.d. 6·6 to 36·2% ± s.d. 8·3.

In comparison to values obtained in normal dogs, only about one‐tenth of the drug excretion in bile and about one‐fifth of the hydrocholeretic effect were obtained after intravenous drug administration to dogs with hepatic impairment induced by CCl4.
Effects of non‐ionic surfactants that modify experimental tuberculosis on lipase activity of macrophages
Authors: D'ARCY HART P. , PAYNE SHEILA N.
Published: July 2012

Six series of non‐ionic surface active polyethylene glycol ethers, whose effects on experimental tuberculosis have previously been correlated with their polyoxyethylene chain lengths, were examined for their influence on the activity of a lipase present in homogenates of normal mouse peritoneal macrophages. The surfactants are concentrated in the lysosomes of macrophages—a cell type in which the host‐parasite confrontation takes place. A preparation of soy bean oil was used as triglyceride substrate; and hydrolysis at pH 4·5 was compared in the presence and absence of surfactant, the products of hydrolysis being assayed by photodensitometry of thin‐layer chromatograms.

The compounds with short polyoxyethylene chains inhibited the release of fatty acid, compared with surfactant‐free standard, more than did those with long chains; and some of the latter showed actual enhancement of release. Accumulation of monoglyceride was observed in the presence of six of the seven long‐chained compounds, but with none of the seven short‐chained compounds.

The similarity between this correlation of chain length of the surfactants with their effect on macrophage lipase activity, and the known correlation of their chain length with their effect on experimental tuberculosis, suggests a possible connection. How this connection might relate to the mechanism of the varying effects on tuberculosis is briefly discussed.
Blockade by phenoxybenzamine of the contractor response produced by agonists in the isolated ileum of the guinea‐pig
Authors: COOK D. A.
Published: July 2012

The effects of various concentrations of phenoxybenzamine (dibenzyline) on the contractor response of the isolated ileum of the guinea‐pig were investigated. The agonists tested were histamine, 5‐hydroxytryptamine (5‐HT), acetycholine and potassium chloride.

In addition, uptake of 14C‐phenoxybenzamine into the ileum was determined as a function of antagonist concentration. The uptake increases sharply at concentrations above 10−6 g/ml, (3×10−6m) and was not saturable at any concentration tested.

In the presence of low concentrations of phenoxybenzamine, the dose‐response curve for histamine undergoes a parallel shift of about 0·5 log units. At higher concentrations of phenoxybenzamine the maximum response is depressed. In the case of the other agonists, the maximum response is depressed as soon as any blockade becomes apparent.

The ease of blockade with phenoxybenzamine is 5‐HT ≥ histamine> acetylcholine ≥ potassium chloride.

These results do not lend support to the ‘spare‐receptor’ hypothesis and may be better explained by the ‘two‐site’ hypothesis of Moran & Triggle (1970).

It may further be concluded that the successful antagonism of potassium‐induced contractions in this preparation lies in the ability of phenoxybenzamine to prevent the action of released acetylcholine. In the case of the contraction induced by 5‐HT, phenoxybenzamine probably interferes with the 5‐HT receptor responsible for neuronal release of acetycholine.
Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor
Authors: GRAHAME‐SMITH D. G.
Published: July 2012

The hyperactivity and hyperpyrexia produced by l‐tryptophan in rats treated with a monoamine oxidase inhibitor was inhibited by chlorpromazine.

Chlorpromazine did not inhibit the increased rate of synthesis of brain 5‐hydroxytryptamine (5‐HT) produced by tryptophan loading.

Hyperactivity and hyperpyrexia were also produced by 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeODMT) in rats. Pretreatment with a monoamine oxidase inhibitor potentiated the hyperactivity response. Pretreatment of rats with p‐chlorophenylalanine did not inhibit hyperactivity produced by 5‐MeODMT.

Chlorpromazine inhibits hyperactivity caused by tryptophan or 5‐MeODMT after monoamine oxidase inhibition either by competition with 5‐HT or 5‐MeODMT, respectively, at receptor sites or by physiological antagonism.
Actions of prostaglandin F2α on the splenic vascular and capsular smooth muscle in the dog
Authors: DAVIES B. N. , WITHRINGTON P. G.
Published: July 2012

The actions of prostaglandin F2α, which is known to be released by the spleen on sympathetic nerve stimulation, have been investigated in the isolated blood perfused spleen of the dog.

Low arterial concentrations of F2α (less than 10 μg/100 ml) caused marked reductions in splenic vascular resistance.

High arterial concentrations of F2α (above 10 μg/100 ml) caused increases in splenic vascular resistance.

Little action on splenic volume was observed by any arterial concentration of F2α.

The reductions in splenic vascular resistance caused by low arterial concentrations of F2α were reversed by blocking doses of phenoxybenzamine.

No appreciable interaction between F2α and the splenic responses to sympathetic nerve stimulation, adrenaline and noradrenaline was observed.

The role of the prostaglandins released by the spleen is discussed.
Investigation of the mechanism of action of oxotremorine on the guinea‐pig isolated ileum preparation
Authors: COX B. , HECKER SALLY E.
Published: July 2012

The effects of oxotremorine on the guinea‐pig ileum have been investigated to determine whether any component of its action is due to acetylcholine release.

Log dose‐response curves to oxotremorine and acetylcholine were similar and both drugs were competitively antagonized by atropine.

Mipafox potentiated acetylcholine but not oxotremorine.

No evidence of an indirect component of the action of oxotremorine was obtained using various pharmacological procedures (tetrodotoxin, morphine, cooling, procaine and hemicholinium‐3).

Oxotremorine had no effect on acetylcholine release from mipafox treated ileum but decreased the release from physostigmine treated ileum.

It is concluded that oxotremorine acts directly on muscarinic receptors and not by releasing acetylcholine.