bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTS OF PROSTAGLANDINS E1, E2 AND F2α ON THE CUTANEOUS VASCULATURE OF THE RAT
Authors: CHAHL LORIS A. , LADD R.J. 
Published: July 2012

The responses of the rat cutaneous vasculature to prostaglandins E1, E2 and F2α have been investigated by a photomicrographic technique.
Prostaglandin E1 produced transient arterial constriction which was blocked by local pretreatment of preparations with compound 48/80 or methysergide. It was concluded that prostaglandin E1 produced vasoconstriction by release of 5‐hydroxytryptamine (5‐HT) from mast cells. The magnitude of the vasoconstrictor response appeared to be subject to seasonal variation.
Prostaglandin F2α produced arterial constriction of longer duration which was not blocked by compound 48/80, methysergide or phenoxybenzamine.
Preparations pretreated with prostaglandin F2α were found to be more sensitive to the venous constrictor effect, and less sensitive to the arterial constrictor effect, of noradrenaline.
Prostaglandin E2 produced arterial constriction which was usually partially blocked by compound 48/80 and methysergide and it was concluded that a major component of the vasoconstrictor response to prostaglandin E2 was of the E1 type but some component was of the F2α type.
EFFECTS OF AMINO ACIDS AND CONVULSANTS ON SPONTANEOUS ACTION POTENTIALS IN CEREBELLAR CORTEX SLICES
Authors: OKAMOTO K. , QUASTEL J.H. 
Published: July 2012

Picrotoxin selectively and reversibly suppressed the inhibitory action of γ‐aminobutyric acid (GABA), but not that of glycine, taurine or β‐alanine, on the frequency of spontaneous spike discharges in guinea‐pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or β‐alanine but had no effect on that of GABA.
GABA, glycine, taurine and β‐alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine.
Studies of the dose‐response relations indicated a competition between the amino acid and the convulsant at a common receptor site.
Kinetic analyses of the dose‐response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for β‐alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or Picrotoxin.
Mixtures of glycine with taurine or β‐alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects.
THE INHIBITION BY GLUCAGON OF THE VASOCONSTRICTOR ACTIONS OF NORADRENALINE, ANGIOTENSIN AND VASOPRESSIN ON THE HEPATIC ARTERIAL VASCULAR BED OF THE DOG
Authors: RICHARDSON P.D.I. , WITHRINGTON P.G. 
Published: July 2012

The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided.
Dose‐dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intraarterial injections of noradrenaline, angiotensin and vasopressin.
Single injections of glucagon (100 μg, i.a.) caused a transient significant fall in HAVR of 19.9 ± 3.2%, and infusions of 25 μg/min of glucagon intra‐arterially caused maintained reductions in HAVR of 16.9 ± 4.2%.
After single injections of 100 μg glucagon intra‐arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85–95%. Recovery occurred in 8–10 minutes.
Intra‐arterial infusions of glucagon, 2.5–50.0 μg/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions.
Dose‐response curves to the constrictor agents were constructed before, during and after intraarterial infusions of 25 μg/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response.
Infusions of glucagon shifted the dose‐response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one‐half.
A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon.
It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.
THE DIFFERENT EFFECTS OF D‐600 (METHOXYVERAPAMIL) ON THE RELEASE OF ADRENAL CATECHOLAMINES INDUCED BY ACETYLCHOLINE, HIGH POTASSIUM OR SODIUM DEPRIVATION
Authors: PINTO J.E.B. , TRIFARÓ J.M. 
Published: July 2012

Bovine adrenal glands were perfused with Locke solution and catecholamine release was induced by acetylcholine, by a depolarizing concentration of potassium, or by omission of sodium from the perfusion fluid.
D‐600 (methoxyverapamil) at the concentration of 30 μm produced a 23% inhibition of catecholamine release evoked by acetylcholine (0.1 mm) in the presence of physostigmine (10 μm).
A concentration of D‐600 of 0.3 mm produced 86% and 85% inhibition in the output of catecholamines in response to acetylcholine and high potassium respectively.
D‐600 (0.3 mm) failed to block the release of catecholamines evoked by sodium deprivation.
The results suggest the involvement of intracellular calcium in the exocytotic release of catecholamines induced by sodium omission.
MECHANISM OF NEUROTOXICITY OF CARDIOTONIC GLYCOSIDES
Authors: GAITONDÉ B.B. , JOGLEKAR S.N. 
Published: July 2012

1In cats intracerebroventricular administration of 5, 10, 20 μg of peruvoside, a cardiac glycoside obtained from the plant, Thevetia neriifolia, and 10 and 20 μg of ouabain, produced marked neurotoxicity. This was dose‐related.2Prior administration of reserpine (2 mg/kg i.m., 500 μg i.c.v.) or tetrabenazine (25 mg/kg i.v., 50 mg/kg i.v. and 2 mg/kg i.c.v.) suppressed the neurotoxicity, but lithium carbonate (100 mg/kg i.p., 2 mg i.c.v.) and haloperidol (200 μg i.c.v.) were ineffective.3Prior administration of 2‐bromolysergic acid diethylamide (BOL‐148, 200 μg i.c.v.) or p‐chlorophenylalanine (PCPA) (400 mg/kg i.p.) suppressed the neurotoxicity induced by peruvoside and ouabain.4Perfusion of the lateral ventricles of cats with 10, 20 and 30 μg of peruvoside or ouabain produced a massive release of 5‐hydroxytryptamine (5‐HT). This was dose‐related. Prior administration PCPA suppressed the release of 5‐HT.5The results of the findings indicate the involvement of 5‐HT in the genesis of neurotoxicity induced by peruvoside or ouabain.
THE ROLE OF BACTERIAL CONTAMINATION IN THE ISOLATION OF APPARENT ANTI‐INFLAMMATORY FACTORS FROM RABBIT ANTI‐LYMPHOCYTIC SERUM
Authors: MAGUIRE E.D. , WALLIS R.B. 
Published: July 2012

1Rabbit anti‐guinea‐pig lymphocytic serum was fractionated by gel filtration to obtain partially purified materials possessing anti‐inflammatory activity. The pharmacological properties of these materials were then studied.2Two fractions were found which reproducibly contained significant activity. One of these activities caused inflammation at the site of injection and was associated with high molecular weight protein (200,000). The other activity was found in a low molecular weight fraction but was shown to be due to small amounts of endotoxin from Gram negative bacteria. These organisms contaminated the fractions in spite of the recommended precautions for gel filtration having been taken.3The endotoxin‐containing fraction completely abolished leucocyte infiltration into the rat foot which had been injected with kaolin. It had no apparent effect on circulating haemolytic complement. It caused maximal elevation of serum 11‐hydroxycorticosteroid concentrations and was found to cause the release of pharmacologically active amines. Many of the previously reported naturally occurring anti‐inflammatory substances have similar pharmacological properties to those of the endotoxin‐containing fraction.4It was concluded that doubt will exist about the presence of anti‐inflammatory factors in mammalian body fluids unless stringent precautions are taken to exclude measurable bacterial contamination.5These experiments also cast doubt on the validity of accepted procedures for excluding microbial growth from columns used in the fractionation of serum.
THE EFFECT OF CONFORMATIONALLY RESTRICTED AMINO ACID ANALOGUES ON THE FROG SPINAL CORD in vitro
Authors: NICOLL R.A. 
Published: July 2012

1The isolated spinal cord of the frog (Rana pipiens) was used to examine the structural requirement for the activity of neutral amino acids. The potencies of the aliphatic amino acids, γ‐aminobutyric acid (GABA), β‐alanine and glycine were compared with the potencies of conformationally restricted cyclopentane and cyclohexane amino acid analogues. Both motoneurone hyperpolarizing and primary afferent depolarizing activity were examined in this study.2On motoneurones β‐alanine was the most potent aliphatic amino acid and glycine the least potent. Of the substituted aminocyclopentane carboxylic acids, that compound with a separation of amino and carboxylic acid groups closest to that of the extended GABA molecule (4.74 Å) had a potency similar to GABA. As the separation decreased the hyperpolarizing activity fell off rapidly. The substituted aminocyclohexane carboxylic acids were generally inactive even at a concentration of 10 mm.3Strychnine blocked the motoneurone hyperpolarizing responses to all compounds with a distance between the amino and carboxylic acid groups of 3.66 Å or less, but did not block the response of compounds with a distance of 4.08 Å or greater. Picrotoxin and bicuculline antagonized all the responses to varying degrees and therefore were of little value in characterizing the responses.4On the primary afferents GABA was the most potent aliphatic amino acid and glycine the least potent. The substituted aminocyclohexane carboxylic acids were generally inactive on primary afferents. The response of the substituted aminocyclopentane carboxylic acid whose separation of amino and carboxylic acid groups was closest to that of the extended GABA molecule was most similar to the GABA response. However, (±)‐cis‐3‐aminocyclopentane‐carboxylic acid (separation=4.08 Å), which mimicked the action of GABA on motoneurones, closely mimicked the depolarizing action of β‐alanine on primary afferents.5The findings suggest that the hyperpolarizing GABA receptor on motoneurones will accept a molecule whose amino and carboxylic acid groups are separated by a distance of 4.08 Å or greater while the glycine receptor will accept a compound with a distance of 3.66 Å or less. The depolarizing GABA receptors on primary afferents appear to be more selective since they are not activated by (±)‐cis‐3‐aminocyclopentane carboxylic acid (separation=4.08 Å), while the motoneurone receptors are.
REPEATED CHLORPROMAZINE ADMINISTRATION INCREASES A BEHAVIOURAL RESPONSE OF RATS TO 5‐HYDROXYTRYPTAMINE RECEPTOR STIMULATION
Authors: GREEN A.R. 
Published: July 2012

1The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by l‐tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5‐hydroxytryptamine (5‐HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and l‐tryptophan administration 24 h after the final dose of chlorpromazine.2One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/l‐tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and l‐tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose.3Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioural responses to the suggested 5‐HT agonist 5‐methoxy N,N‐dimethyltryptamine (2 mg/kg) on day 5.4Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5‐hydroxytryptamine (5‐HT) concentration on day 5, but no difference in the rate of brain 5‐HT synthesis or the rate of 5‐HT accumulation after tranylcypromine and l‐tryptophan administration.5There is some evidence that chlorpromazine blocks 5‐HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5‐HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5‐HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5‐HT receptors.
THE EFFECT OF CATECHOLAMINES ON THE in vivo AND in vitro RESPONSES OF THE CAT LUNG DURING ANAPHYLAXIS
Authors: MITCHELL H.W. , SPARROW M.P. 
Published: July 2012

Anaphylaxis in the lung of cats actively sensitized to Ascaris antigen has been investigated in vivo and in vitro.
In vivo there was a 100% increase in airways resistance and a 50% decrease in dynamic lung compliance following intravenous challenge with Ascaris antigen. Prostaglandin F2α induced similar changes but with histamine only dynamic lung compliance was affected. (‐)‐Isoprenaline prevented these prostaglandin F2α‐ and histamine‐induced changes and caused a delay of about 2 min in the onset of the mechanical changes following anaphylactic challenge.
In vitro the isolated lung strip contracted within seconds of challenge whereas there was a delay of 2 to 3 min in the onset of the tracheal anaphylactic response. (‐)‐Isoprenaline, (‐)‐adrenaline and (+)‐noradrenaline reduced the magnitude of anaphylactic contractions of the isolated trachea but did not significantly affect those of the isolated lung strip. This indicated lack of inhibition of mediator release from the lung parenchyma.
Histamine was released from sensitized lung fragments following challenge with the Ascaris extract. This release constituted 6.3% of the total tissue histamine and was not inhibited by (‐)‐isoprenaline (1 μM).
(‐)‐Isoprenaline abolished 5‐hydroxytryptamine (5‐HT)‐induced contractions of the isolated trachea but not those elicited in response to acetylcholine. The isolated lung strip responses to histamine, prostaglandin F2α and 5‐HT were highly resistant to inhibition by (‐)‐isoprenaline.
RESPIRATORY AND CIRCULATORY EFFECTS OF SAXITOXIN IN THE CEREBROSPINAL FLUID
Authors: BORISON H.L. , McCARTHY L.E. 
Published: July 2012

In cats anaesthetized with pentobarbitone, saxitoxin and, on a few occasions, tetrodotoxin were injected into a lateral cerebral ventricle or into the subarachnoid space of the lower brain stem. Observations were made on frequency and tidal volume of breathing, on CO2 responsiveness and on electrical responsiveness of the respiratory centre. Effects on the blood pressure were observed simultaneously.
A single large dose of toxin, e.g., 250 ng, produced within minutes apneustic breathing and a rise in blood pressure which were converted rapidly to respiratory failure and hypotension. In contrast, repeated small doses, e.g., 25 ng, yielded only progressive slowing of the respiration together with circulatory hypotension. Bulbar depression was produced as effectively by subarachnoid injection as by intraventricular injection of the toxins. Onset of action was detectable within seconds.
Slowing of the respiration occurred independently of change in tidal volume and whether or not the vagus nerves were cut. The reduction in breathing frequency is attributed to direct toxin‐induced depression of the central respiratory oscillator.
Steady‐state measurements of tidal volume at controlled levels of alveolar CO2 pressure in intermediate stages of respiratory depression showed that the toxins produced an increase in CO2 stimulation threshold as well as a reduction in gain of CO2 responsiveness, whether or not the vagus nerves were cut. Carotid arterial chemoreceptor reactivity to O2 was demonstrable when central sensitivity to CO2 was depressed. These effects are attributed to a direct influence of the toxins upon the brainstem CO2‐tidal volume controller.
Responsiveness of the medullary inspiratory centre to electrical stimulation persisted after the failure of spontaneous breathing was caused by the toxins. Conversely, restitution of electrical responsiveness preceded the reappearance of spontaneous respiratory activity in the recovery phase of toxic depression. Circulatory effects paralleled the changes in respiratory behaviour.
On the basis of the relatively prompt and discrete alterations in the central respiratory and circulatory control mechanisms produced by saxitoxin and tetrodotoxin placed in the cerebrospinal fluid, it is concluded that the agents rapidly penetrated to deep target loci in the lower brain stem.
EFFECT OF APOMORPHINE AND ITS N‐PROPYL HOMOLOGUE ON ETHANOL WITHDRAWAL HEAD TWITCHES IN MICE
Authors: PEARL J. , WOODWARD W.A. 
Published: July 2012

Collier, Hammond & Schneider (1976) reported that apomorphine, given orally, decreased the incidence of head twitches induced by ethanol withdrawal. These results were confirmed in the present study. Moreover, the N‐propyl homologue of apomorphine was about 45 times more potent than apomorphine in affecting head twitching.Discussion Apomorphine inhibited head twitching in mice after ethanol withdrawal in accordance with the results of Collier et al. (1976). That the N‐propyl compound was considerably more potent than apomorphine in preventing head twitching agrees with the majority of results of previous studies in which different tests were used (Ashton et al., 1976; Pearl, 1977).
THE MODE OF ACTION OF TETRABENAZINE ON PERIPHERAL NORADRENERGIC NERVES
Authors: TOMLINSON D.R. 
Published: July 2012

Tetrabenazine (100 mg/kg i.p. in rats) greatly decreased catecholamine‐induced histofluorescence in the iris, hepatic portal vein, inferior vena cava and mesenteric blood vessels 4 h after injection. Fluorescence returned to normal by 24 h after injection.
The extent of this depletion (4 h after tetrabenazine) was similar to that seen 18 h after reserpine (0.5 mg/kg i.p.)
Incubation of tissues taken from rats 4 h after this dose of tetrabenazine with noradrenaline 5 × 10−6M restored the intraneuronal fluorescence as well as the electron density of noradrenergic vesicle cores viewed with the electron microscope. No such repletion was seen on incubation of tissues from reserpine‐treated rats with noradrenaline under the same conditions.
Incubation of tetrabenazine‐treated hepatic portal veins with noradrenaline also reinstated the normal response to electrical stimulation of the intramural nerves. This did not occur with reserpine‐treated veins.
The interpretation that tetrabenazine exerts a reversible depleting effect on the noradrenergic vesicle is supported by the demonstration that it exerts no monoamine oxidase inhibition.
TRANSIENT CHANGES IN PLASMA DIGOXIN CONCENTRATION AND THE DEVELOPMENT OF CARDIOTOXICITY
Authors: CHAPPLE D.J. , HUGHES R. , JOHNSON B.F. 
Published: July 2012

Eight dogs were given two infusions of digoxin 0.1 mg/kg, one over 9 min and the other one over 90 min in a randomized sequence, allowing at least 12 days between each experiment.
Digoxin plasma profiles reflected the rate of digoxin infusion, the peak concentration of drug attained at the end of each infusion being considerably higher but more transient after the 9 min than after the 90 min transfusion.
Digoxin reduced the amount of acetylstrophanthidin required to produce electrocardiographic evidence of cardiotoxicity. This increase in cardiac sensitivity at 150 and at 360 min after the start of the digoxin infusion was independent of rate of infusion.
These results suggest that the development of cardiotoxicity is dependent upon the quantity of digoxin delivered into the systemic circulation regardless of the plasma concentration.
By inference, cardiotoxicity is related solely to the amount and not the rate of absorption from a given dose of digoxin.
A PHARMACOLOGICAL STUDY OF THE SPONTANEOUS CONVULSIVE ACTIVITY INDUCED BY 1,2‐DIHYDROXYBENZENE (CATECHOL) IN THE ANAESTHETIZED MOUSE
Authors: ANGEL A. , CLARKE K.A. , DEWHURST D.G. 
Published: July 2012

The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug‐treated and control animals, or by studying the effects of various drugs on the total whole body activity.
The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the α‐ and β‐adrenoceptor blocking drugs.
5‐Hydroxytryptamine (5‐HT) could possibly be important, though results with drugs which either change brain 5‐HT levels, or block 5‐HT receptors were inconsistent.
γ‐Aminobutyric acid also appears not to be involved in the mechanism of action of catechol.
The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions.
THE DEPENDENCE OF THE LIPID BILAYER MEMBRANE: BUFFER PARTITION COEFFICIENT OF PENTOBARBITONE ON pH AND LIPID COMPOSITION
Authors: MILLER K.W. , YU S‐C. T. 
Published: July 2012

The membrane/buffer partition coefficient of [14C]‐pentobarbitone has been determined as a function of the lipid composition of bilayer membranes.
A new technique based on ultrafiltration gave comparable results to conventional techniques but required less time for equilibration.
The membrane/buffer coefficient was independent of pentobarbitone concentration in the range studied.
The apparent partition coefficient varied with pH and was a linear function of the degree of dissociation of pentobarbitone.
Both the charged and uncharged forms of pentobarbitone partitioned into the membrane, the latter to a much greater extent than the former.
At low pH the highest partition coefficient observed was in egg phosphatidylcholine bilayer membranes.
Incorporation of cholesterol or phosphatidic acid into phosphatidylcholine membranes greatly reduced the partition coefficient.
High pressures do not greatly change these partition coefficients.
DO CENTRAL DOPAMINE RECEPTORS HAVE A PHYSIOLOGICAL ROLE IN THERMOREGULATION?
Authors: COX B. , LEE T.F. 
Published: July 2012

Core and tail skin temperature was measured in rats which had guide cannulae implanted into their brains to allow drug injections directly into the preoptic anterior hypothalamus.
Apomorphine and dopamine (10 μg in 1 μl) injected into the area of the preoptic anterior hypothalamus caused a fall in core temperature which was preceded by a rise in tail skin temperature.
The decrease in core temperature following central injection of either apomorphine or dopamine was significantly reduced by pretreating rats for 2 h with pimozide (0.5 mg/kg i.p.).
Bilateral intrahypothalamic injection of pimozide (0.5 μg in 1 μl) significantly reduced the hypothermic effect of systemic apomorphine (1.25 mg/kg i.p.).
Control rats placed 65 cm below a 250 W infrared lamp responded with vasodilatation of tail skin blood vessels as indicated by an increase in tail skin temperature. Pimozide pretreatment (0.5 mg/kg i.p.) significantly reduced this response.
These results suggest that the preoptic anterior hypothalamus contains dopamine receptors which mediate hypothermia in rodents and raise the possibility that endogenous dopamine has a physiological role in thermoregulation.