bluuebunny/crossref_metadata_2025_split huggingface dataset:
FACTORS AFFECTING THE CEREBROVASCULAR RESPONSE TO NORADRENALINE IN THE DOG
Authors: JAMES I.M. , MACDONELL LINDSAY 
Published: July 2012

Noradrenaline infused into the internal carotid artery of the dog (0.01–1 μg kg−1 min−1) constricts the blood vessels of the cortex. This constriction is mediated by the action of noradrenaline on α‐adrenoceptors of the cerebral arteries.
Intravenous (1 μg kg−1 min−1) or intra common carotid arterial (0.01–1 μg kg−1 min−1) infusions of noradrenaline cause an increase in cortical blood flow that can be dissociated from changes in blood pressure.
The effect of intravenous noradrenaline on the cortical blood vessels and metabolism is blocked by high PaCO2 levels, or by the prior administration of (±)‐propranolol. (+)‐Propranolol is without such effect.
Following section of both vagi and both sinus nerves, intravenous noradrenaline fails to cause an increase in cortical blood flow.
In another series of animals the area of the carotid bifurcation was vascularly isolated and perfused with blood from a second dog. Chemoreceptor and baroreceptor activity was shown to be intact.
Administration of 5% CO2 to the donor dog caused an increase in cerebral blood flow in the recipient dog.
Administration of intravenous noradrenaline (1.0 μg kg−1 min−1) to the donor animal caused an increase in cerebral blood flow, cerebral O2 and glucose utilization of the recipient.
Administration of 5% CO2 and intravenous (—)‐noradrenaline (1.0 μg kg−1 min−1) caused a further increase in flow and metabolism.
This evidence suggests that the cerebrovasodilatation observed following intravenous noradrenaline is reflex and is triggered by chemoreceptor activity.
The evidence also suggests that the antagonism of the cortical dilatory effects of intravenous noradrenaline by raised PaCO2 in the intact animal must be at a site different from the peripheral chemoreceptors.
THE EFFECTS OF PROSTAGLANDINS ON GUINEA‐PIG ISOLATED INTESTINE AND THEIR POSSIBLE CONTRIBUTION TO MUSCLE ACTIVITY AND TONE
Authors: BENNETT A. , ELEY K.G. , STOCKLEY HELEN L. 
Published: July 2012

Prostaglandins F1α and F2α caused contraction of the longitudinal muscle of both guinea‐pig isolated ileum and colon, apparently by acting directly on the muscle and on cholinergic nerves. They had little effect on ileal circular muscle.
Prostaglandins E1 and E2 caused contraction of the longitudinal muscle of guinea‐pig isolated colon, apparently by acting directly on the muscle and on excitatory nerves which are non‐cholinergic. Prostaglandin E1 seems more effective than E2 in stimulating these nerves.
It seems likely that prostaglandin release in vitro maintains the tone of the longitudinal muscle of guinea‐pig colon, whereas release of a prostaglandin E compound inhibits circular muscle tone.
LACK OF CARDIAC OR BRONCHODILATOR TACHYPHYLAXIS TO ISOPRENALINE IN THE DOG
Authors: MINATOYA H. , SPILKER B.A. 
Published: July 2012

Tachyphylaxis to heart rate and bronchodilator effects of (±)‐isoprenaline was studied in anaesthetized open‐chest dogs by 5 procedures.
Heart rate responses to a series of intravenous injections of isoprenaline were essentially unchanged before and after a 15 min infusion of isoprenaline (at 3 doses).
Heart rate and bronchodilator responses in the same animal to an intravenous injection of isoprenaline were not significantly different before and after a 30 min infusion of isoprenaline (at 2 doses).
Heart rate responses were relatively constant to an isoprenaline injection given every 30 min during a 4 h infusion of isoprenaline (at 3 doses), but the magnitude of the response was smallest for the largest infusion dose (highest background heart rate) and greatest for the smallest infusion dose (lowest background heart rate).
Heart rate and bronchodilator responses in the same animal to isoprenaline were relatively constant during a 5 h infusion of isoprenaline (at 2 doses).
Bronchodilator responses to intratracheally administered isoprenaline aerosol were essentially unchanged during a 4–5 h period using various doses and procedures.
Tachyphylaxis to the heart rate or bronchodilator effects of isoprenaline was not observed. The present data give no support to the hypothesis that tachyphylaxis to isoprenaline aerosols is an important mechanism in asthma mortality.
THE OFFSET OF MORPHINE TOLERANCE IN RATS AND MICE
Authors: COX B.M. , GINSBURG M. , WILLIS JULIA , DAVIES J.K. 
Published: July 2012

In rats and mice made tolerant to morphine by pretreatment with the drug, the shift to the right of the log dose/analgesic response line for morphine from its position in naive animals occurs without significant change in slope provided that sufficient time is allowed for elimination of pretreatment drug.
Responsiveness to the analgesic effects of morphine, given together with cycloheximide to prevent reinforcement of tolerance, was measured in rats (paw pressure method) and mice (hot plate method) at intervals during 1–23 days following cessation of a variety of regimens of tolerance‐inducing drug treatments.
A biphasic pattern of recovery of responsiveness was observed, which was independent of the regimen or the drug (morphine, methadone or diamorphine) used to induce tolerance. Estimates of the rates of the first, fast phase are imprecise but the rate of the second phase of offset, from 4th day after cessation of pretreatment had, in rats, a mean half‐time of 13.2 ± 0.53 days‐for all pretreatments combined, there being no significant differences between the various pretreatment regimens employed. In mice, similarly, a biphasic recovery of analgesic responsiveness was seen after morphine pretreatment, the mean half‐time of the slower phase being 17.4 days.
Precipitation of an acute withdrawal syndrome in rats by naloxone HC1 given 6 h after the final injection of a tolerance‐inducing treatment with morphine did not affect the subsequent rate of recovery from tolerance.
During the period following a tolerance‐inducing pretreatment with morphine in mice, the rate of attenuation of the naloxone‐evoked jumping response was faster than the rate of offset of tolerance.
INHIBITION OF IMMEDIATE HYPERSENSITIVITY REACTIONS IN LABORATORY ANIMALS BY A PHENANTHROLINE SALT (ICI 74,917)
Authors: EVANS D.P. , THOMSON D.S. 
Published: July 2012

The activity of a new anti‐allergic compound, I.C.I. 74,917, has been studied in the rat, mouse and guinea‐pig.
Following intravenous administration, I.C.I. 74,917 inhibits in a dose‐dependent manner passive cutaneous anaphylaxis induced in rats and mice by heat‐labile homocytotropic antibody. In rats, its potency is approximately 300 times that of disodium cromoglycate.
To achieve maximal inhibition, it is necessary to administer I.C.I. 74,917 at the same time as antigenic challenge; dosing before or after challenge has much less effect.
Liberation of histamine, provoked by the antigenic challenge of mast cells passively sensitized in vitro by IgE‐like antibody, is reduced in the presence of I.C.I. 74,917.
Intravenous administration of the compound has no significant effect upon local blueing reactions provoked in the rat by intradermal injection of histamine, 5‐hydroxytryptamine or Compound 48/80. It has only a slight effect at high doses upon passive cutaneous anaphylaxis induced in the rat by heat‐stable homocytotropic or heterologous (guinea‐pig) antibodies.
Although not a bronchodilator in the guinea‐pig, I.C.I. 74,917 partially inhibits systemic anaphylaxis. A consistent reduction in the severity of antigen‐induced bronchospasm was demonstrated in the Konzett‐Rössler preparation at doses comparable to those inhibiting passive cutaneous anaphylaxis in the rat. However, there was only slight inhibition of passive cutaneous anaphylaxis in the guinea‐pig.
I.C.I. 74,917 itself induces bronchospasm when administered to anaesthetized guinea‐pigs or to a guinea‐pig isolated lung preparation. This effect is reversed by salbutamol, but is not prevented by the prior administration of mepyramine, atropine or methysergide.
These results indicate that in the rat, mouse and guinea‐pig, I.C.I. 74,917 is a potent inhibitor of certain types of immediate hypersensitivity reactions.
INHIBITORY EFFECTS OF CLONIDINE AND BS 100‐141 ON RESPONSES TO SYMPATHETIC NERVE STIMULATION IN CATS AND RABBITS
Authors: PACHA W. , SALZMANN R. , SCHOLTYSIK G. 
Published: July 2012

In pithed cats, the spinal sympathetic outflow was stimulated preganglionically at segments C7 and T1 and heart rate responses and nictitating membrane tone were measured in parallel.
Clonidine and a related drug, BS 100‐141 (N‐amidino‐2‐(2,6‐dichlorophenyl)acetamide hydrochloride), caused a dose‐dependent inhibition of the stimulation‐induced tachycardia but did not inhibit responses of the nictitating membrane. The inhibition of heart rate was antagonized by the α‐adrenoceptor blocking drug, phentolamine.
In isolated hearts of rabbits, noradrenaline release in response to adrenergic nerve stimulation was reduced by clonidine and BS 100‐141 and the effect was antagonized by phentolamine.
The results support the view that presynaptic α‐adrenoceptors are involved in the regulation of transmitter release from adrenergic nerves. Cardiac adrenergic nerves appear more sensitive to α‐adrenoceptor‐mediated inhibition of impulse transmission than the sympathetic nerves to the nictitating membrane.
EFFECT OF FENFLURAMINE ON 5‐HYDROXYTRYPTAMINE UPTAKE AND RELEASE BY RAT BLOOD PLATELETS
Authors: BUCZKO W. , DE GAETANO G. , GARATTINI S. 
Published: July 2012

(+)‐Fenfluramine reduces the central stores of 5‐hydroxytryptamine (5‐HT) by a poorly understood mechanism.
Rat blood platelets have been used in this study as a simple model for serotoninergic nerve endings.
(+)‐Fenfluramine shows a dual effect: it inhibits the uptake of [14C]‐5‐HT by platelets and it releases newly absorbed [14C]‐5‐HT from platelets.
The inhibition of [14C]‐5‐HT uptake induced by (+)‐fenfluramine appears very rapidly, is concentration‐dependent and seems not to be competitive. (+)‐Fenfluramine is ten times less effective than chloroimipramine but ten times more effective than (+)‐amphetamine; (+)‐fenfluramine is more active than its (‐)‐isomer or its metabolite norfenfluramine ((+)‐ or (‐)‐form).
The release of [14C]‐5‐HT from platelets induced by (+)‐fenfluramine is concentration‐dependent but increases with increased incubation time. Both chloroimipramine and (+)‐amphetamine are in comparison very poor release inducers; (+)‐fenfluramine is more active than its (‐)‐isomer or its metabolites.
The effect on [14C]‐5‐HT uptake exerted by (+)‐fenfluramine and chloroimipramine in vitro could not be observed in vivo.
The observed effect of fenfluramine on the uptake and release of 5‐HT may explain the lowering action of fenfluramine on the brain 5‐HT level, an effect considered of importance for the anorectic effect of this drug.
ASSESSMENT IN THE GUINEA‐PIG ILEUM AND MOUSE VAS DEFERENS OF BENZOMORPHANS WHICH HAVE STRONG ANTINOCICEPTIVE ACTIVITY BUT DO NOT SUBSTITUTE FOR MORPHINE IN THE DEPENDENT MONKEY
Authors: HUTCHINSON M. , KOSTERLITZ H.W. , LESLIE FRANCES M. , WATERFIELD ANGELA A. , TERENIUS L. 
Published: July 2012

Four benzomorphans which have potent antinociceptive activity in the hot‐plate and writhing tests in the mouse but do not suppress or precipitate withdrawal symptoms in the morphine‐dependent monkey, have been examined for their pharmacological actions in the guinea‐pig ileum and mouse vas deferens.
In the guinea‐pig ileum their agonist potencies are 1.5 to 400 times greater than that of normorphine or morphine whereas in the mouse vas deferens their potencies relative to morphine are 0.3 to 100. They exhibit no antagonist activity in either preparation. Benzomorphans which substitute for morphine in the morphine‐dependent monkey do not show such differences between their relative potencies in the guinea‐pig ileum and mouse vas deferens.
The relative potencies of the four benzomorphans to inhibit stereospecific [3H]‐dihydromorphine binding by membrane fragments from rat brain, are more closely related to their relative agonist potencies in the mouse vas deferens than to those found in the guinea‐pig ileum.
In order to antagonize the agonist actions of these benzomorphans, naloxone is required in concentrations which are 3 to 7 times higher than those needed for the antagonism of normorphine or morphine or of benzomorphans which suppress abstinence in morphine‐dependent monkeys.
It may be possible to use the three assays, namely, ratio of relative agonist potency in mouse vas deferens to that in guinea‐pig ileum, ratio of relative agonist potency to relative affinity to opiate receptors and the concentration of naloxone required for antagonism, for the prediction of the potential of new compounds to produce physical dependence.
EFFECTS OF DESIPRAMINE ON NEURONAL RESPONSES TO DOPAMINE, NORADRENALINE, 5‐HYDROXYTRYPTAMINE AND ACETYLCHOLINE IN THE CAUDATE NUCLEUS OF THE RAT
Authors: BEVAN P. , BRADSHAW C.M. , SZABADI E. 
Published: July 2012

The sensitivity of single neurones to microelectrophoretically applied dopamine, noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and acetylcholine (ACh) was investigated in the caudate nucleus of the rat, anaesthetized with halothane. Both excitatory and depressant responses could be observed to each of the agonists. There was a high correlation between the direction of responses to dopamine and noradrenaline, whereas there was no significant correlation between the direction of responses to dopamine and ACh.
The effect of desipramine was studied on both excitatory and depressant responses to dopamine, NA and 5‐HT, and on excitatory responses to ACh. Both potentiation and antagonism of neuronal responses to monoamines and ACh could be observed after a brief application of desipramine.
Excitatory responses to glutamate were not affected by desipramine.
The observation that responses to dopamine and NA can be potentiated by desipramine in the caudate nucleus suggests that uptake blockade is not a prerequisite for potentiation.
It is suggested that the potentiation of neuronal responses to dopamine by desipramine may be responsible for the therapeutic efficacy of desipramine in Parkinson's disease.
POTENCY AND SELECTIVITY OF METHYL ANALOGUES OF PROSTAGLANDIN E2 ON RAT GASTROINTESTINAL FUNCTION
Authors: MAIN I.H.M. , WHITTLE B.J.R. 
Published: July 2012

The potency and selectivity of action of prostaglandin E2 and its (15S)‐ or (15R)‐15 methyl and 16,16 dimethyl analogues on gastrointestinal function have been studied in the rat.
The (15S)‐15 methyl and 16,16 dimethyl analogues were 40 times as active as prostaglandin E2 in inhibiting pentagastrin‐stimulated acid secretion on intravenous administration to the anaesthetized rat, and 100 times as active on subcutaneous injection to the chronic fistula rat.
In antisecretory doses, the analogues, like prostaglandin E2, caused bile reflux and, in higher doses, profuse diarrhoea.
The (15S)‐15 methyl and 16,16 dimethyl analogues were at least 30 times as active as prostaglandin E2 in causing changes in intestinal intraluminal pressure in vivo, but were equipotent on isolated smooth muscle.
In equivalent antisecretory doses, the methyl analogues had little effect on systemic arterial blood pressure and resting mucosal blood flow compared with prostaglandin E2.
The (15R) methyl epimer administered parenterally had little effect on gastrointestinal function but brief acid incubation greatly increased its activity.
THE EFFECTS OF PROSTAGLANDINS E1, E2 AND F2αON VAGAL BRADYCARDIA IN THE ANAESTHETIZED MOUSE
Authors: FENIUK W. , LARGE B.J. 
Published: July 2012

In anaesthetized mice prostaglandins E1 and E2 reduced the bradycardia caused by electrical stimulation of the sectioned peripheral vagus nerve; prostaglandin F2α produced only a slight inhibition of the vagal response.
None of the prostaglandins studied affected acetylcholine‐induced bradycardia.
Prostaglandins modify para sympathetic nerve activity in vivo presumably by a pre‐synaptic action.
AN ELECTROPHYSIOLOGICAL ANALYSIS OF THE EFFECTS OF RESERPINE ON ADRENERGIC NEUROMUSCULAR TRANSMISSION
Authors: BENNETT M.R. , MIDDLETON J. 
Published: July 2012

An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles < 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release.
Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%.
Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone.
During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady‐state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train.
These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis.
TIMID SINGLY‐HOUSED MICE: THEIR VALUE IN PREDICTION OF PSYCHOTROPIC ACTIVITY OF DRUGS
Authors: KRŠIAK M. 
Published: July 2012

About 45% of singly‐housed male mice showed timidity (alert postures, running away, defensive postures) instead of aggression on interactions in pairs with group‐housed male mice, though their partners did not show any aggression. The isolation‐induced timidity was stable in repeated interactions. Timid mice also showed locomotion (walking across cage and rearing) and a small amount of sociable activity (sniffing, following partners and climbing over them).
Diazepam (5 mg/kg), chlordiazepoxide (20 mg/kg), chlorpromazine (7.5 mg/kg) and barbitone (60 mg/kg) given orally inhibited the isolation‐induced timidity without reducing other motor activities in the timid mice. Imipramine lessened timidity only in a dose (80 mg/kg) which also decreased other components of behaviour in the timid isolates. (+)‐Amphetamine and lysergic acid diethylamide (LSD) increased the timid response.
Comparison of the inhibition of timid activities with changes in other behaviour occurring at the same time seems a better measure of selective timidity‐reducing effects of drugs than the rota‐rod test.
Diazepam (5 mg/kg) increased sociable and locomotor activities. Barbitone (20 and 60 mg/kg) increased sociable activities; however, the higher dose also evoked some aggression in timid mice.
Behaviour of timid singly‐housed male mice seems to be a good measure for prediction of activity of drugs in relieving anxiety as well as for detection of aggression‐evoking and sociability‐increasing effects of drugs.
MEMBRANE POTENTIAL CHANGES INDUCED BY 5‐HYDROXYTRYPTAMINE IN THE RABBIT SUPERIOR CERVICAL GANGLION
Authors: WALLIS D.I. , WOODWARD B. 
Published: July 2012

Changes in resting membrane potential induced by 5‐hydroxytryptamine (5‐HT) have been measured in the excised ganglion by the sucrose‐gap technique.
5‐HT produced a rapid depolarization, the threshold concentration for depolarization being around 10 μM. With concentrations of 100 μM or greater, repolarization began during the course of the supervision; this was followed by prolonged tachyphylaxis.
Tachyphylaxis was largely avoided by making injections into the superfusion stream. Standard injections of 0.2 μmol 5‐HT dissolved in 0.2 ml of Krebs solution were used routinely and could be given at 20–30 min intervals to evoke relatively constant responses.
The response to an injection consisted of a rapid depolarization, followed by a rapid repolarization and subsequent after‐hyperpolarization. The threshold quantity for depolarization was around 0.01 μmol, while the ED50 estimated from 6 dose‐response curves was 0.12 ± 0.02 μmol (mean ± s.e. mean).
Injections of 5‐HT (0.2 μmol), choline (10 μmol) and acetylcholine (9.9 μmol) produced depolarizations of similar magnitude.
Monoamine oxidase inhibitors failed to alter substantially the amplitude of depolarizations to 5‐HT.
5‐HT depolarizations were unaltered in amplitude when the impermeant anion benzenesulphonate was substituted for the chloride ion in Krebs solution, but were initially markedly reduced in amplitude in a sodium‐deficient medium; some recovery of the response subsequently occurred. The depolarization which persisted in sodium‐deficient solutions was much reduced or abolished when calcium ions were then removed from the superfusion medium. Removal of either calcium ions alone or potassium ions from the superfusion fluid did not reduce depolarization amplitude.
The after‐hyperpolarization was abolished in sodium‐deficient solutions, usually increased in potassium‐free solutions, reduced or abolished by ouabain or nicotine, but unaffected by calcium‐free solutions.
A depolarizing action of 5‐HT on presynaptic terminals in the ganglion appears probable.
ANTIOXOTREMORINE ACTION OF PROPRANOLOL
Authors: GANGULY D.K. 
Published: July 2012

The influence of propranolol on the neuromuscular, tremor‐producing and muscarinic effects of oxotremorine was examined.
In the isolated rat phrenic nerve‐diaphragm preparation the neuromuscular blocking effect of oxotremorine was inhibited by propranolol in a dose‐dependent manner.
Propranolol intensified the paralytic effect of tubocurarine in the rat diaphragm and prevented antagonism of tubocurarine paralysis by tetraethylammonium.
Propranolol was devoid of any curare‐like effect in the isolated rectus abdominis muscle of the frog.
Vasodepressor responses to oxotremorine in rats and spasmogenic responses to oxotremorine in guinea‐pig ileum were not antagonized by propranolol.
A dose‐dependent antagonism of oxotremorine‐induced tremor in mice was observed after pretreatment with propranolol and it is suggested that this effect is due to an antagonism of a presynaptic effect of oxotremorine at skeletal neuromuscular junctions.
EFFECTS OF 5,7‐DIHYDROXYTRYPTAMINE ON AN IDENTIFIED 5‐HYDROXYTRYPTAMINE‐CONTAINING NEURONE IN THE CENTRAL NERVOUS SYSTEM OF THE SNAIL Helix pomatia
Authors: OSBORNE N.N. , PENTREATH V.W. 
Published: July 2012

The effect of 5,7‐dihydroxytryptamine (5,7‐DHT) on an identified 5‐hydroxytryptamine (5‐HT)‐containing neurone in the CNS of the snail was studied by histochemical, biochemical and electrophysiological methods.
Low concentrations of 5,7‐DHT decreased the endogenous 5‐HT content of the neurone without affecting the amino acids, while relatively large amounts of the drug proportionately lowered 5‐HT and in addition slightly decreased the tryptophan and methionine content of the cell.
5,7‐DHT blocked the uptake of [3H]‐5‐HT into the neurone; the close analogue 5,6‐DHT was more potent.
As well as slightly influencing the accumulation of [3H]‐tryptophan by the neurone 5,7‐DHT inhibited the metabolism of this amino acid to form 5‐HT, probably by affecting the enzyme tryptophan‐hydroxylase.
5,7‐DHT produced a postsynaptic blockade of transmission from the neurone by blocking the 5‐HT receptors of the follower neurones. This effect appeared to be specific for 5‐HT receptors.
The data support the idea that 5,7‐DHT is neurotoxic for indoleamine‐containing neurones.