bluuebunny/crossref_metadata_2025_split huggingface dataset:
MECHANISM OF THE INDIRECT SYMPATHOMIMETIC EFFECT OF 5‐HYDROXYTRYPTAMINE ON THE ISOLATED HEART OF THE RABBIT
Authors: FOZARD J.R. , MWALUKO G.M.P. 
Published: July 2012

Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5‐hydroxytryptamine (5‐HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP).
The cardiac stimulant effects of 5‐HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist.
Responses to 5‐HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6‐hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated.
Rapid, reversible and selective tachyphylaxis to 5‐HT was demonstrated during perfusion with 5‐HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5‐HT were also reduced.
Perfusion of hearts with colchicine inhibited stimulant responses to 5‐HT and DMPP but had little effect on responses to noradrenaline or tyramine.
Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5‐HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine.
Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5‐HT and DMPP unaffected.
5‐HT, tyramine and DMPP evoked 3H‐release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]‐(–)‐noradrenaline. The pattern of release evoked by 5‐HT was similar to that of DMPP but differed from that of tyramine.
Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H‐overflow after tyramine but greatly inhibited that evoked by 5‐HT and DMPP.
The results confirm that the stimulant effects of 5‐HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium‐dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).
EVIDENCE CONCERNING THE INVOLVEMENT OF 5‐HYDROXYTRYPTAMINE IN THE LOCOMOTOR ACTIVITY PRODUCED BY AMPHETAMINE OR TRANYLCYPROMINE PLUS l‐DOPA
Authors: GREEN A.R. , KELLY P.H. 
Published: July 2012

Pretreatment of rats with p‐chlorophenylalanine (PCPA; 2 × 200 mg/kg) decreased the concentration of 5‐hydroxytryptamine (5‐HT) in the brain. It also decreased the locomotor activity produced by tranylcypromine plus l‐DOPA administration 24 h after the second dose of PCPA.
Pretreatment with p‐chloroamphetamine, which produced a similar decrease in brain 5‐HT concentrations did not decrease the locomotor response to tranylcypromine and l‐DOPA.
PCPA pretreatment decreased the rise in the concentration of DOPA and dopamine in the brain following tranylcypromine and l‐DOPA, suggesting its effect on the dopamine‐induced locomotor activity was the result of this drug diminishing dopamine formation in the brain, probably by inhibiting l‐DOPA uptake.
The locomotor activity produced by tranylcypromine and L‐DOPA was not decreased by pretreatment 6 h earlier with disulfiram (400 mg/kg). This argues against the locomotor activity being due to noradrenergic stimulation.
PCPA pretreatment did not alter amphetamine‐induced stereotypy or the circling behaviour in unilateral nigro‐striatal lesioned rats.
THE INHIBITORY EFFECT OF GALLAMINE ON MUSCARINIC RECEPTORS
Authors: CLARK A.L. , MITCHELSON F. 
Published: July 2012

The inhibitory effect of gallamine (1.1 μM‐1.1 mM) on negative inotropic responses to acetylcholine (ACh) or carbachol (CCh) was investigated in isolated electrically stimulated atria of the guinea‐pig. Gallamine caused parallel rightward shifts of the dose‐response curves to the agonists, with no depression of the maximal response.
Gallamine (0.11‐1.1 mM) produced a greater degree of antagonism towards CCh than towards ACh. With either agonist, the degree of antagonism produced by gallamine in high concentrations was less than that expected for a competitive antagonist.
Similar findings were made when either negative inotropic or chronotropic responses were recorded in spontaneously beating guinea‐pig atria. The inhibitory effect of gallamine against the negative inotropic response to cholinomimetics in electrically stimulated atria was not altered either in the presence of propranolol (17 μM) or in atria obtained from guinea‐pigs pretreated with diisopropylphosphorofluoridate (DFP) (12.5 μmol/kg, in divided doses over 3 days).
When ACh was used as the agonist, combination of gallamine with atropine (0.05‐0.4 μM) produced dose‐ratios which were less than expected for combination of two competitive antagonists. The same phenomenon was observed in atria obtained from guinea‐pigs pretreated with DFP.
It is suggested that the antagonism produced by gallamine is a type of non‐competitive inhibition, which has been termed ‘metaffinoid antagonism’. An antagonist of this type allosterically alters the affinity of the agonist for its binding site, rather than changing the effectiveness of the agonist‐receptor interaction.
ANAESTHETICS DEPRESS THE SENSITIVITY OF CORTICAL NEURONES TO l‐GLUTAMATE
Authors: RICHARDS C.D. , SMAJE J.C. 
Published: July 2012

The effects of general anaesthetics on the responses of neurones to iontophoretically applied l‐glutamate have been examined in slices of the guinea‐pig olfactory cortex in vitro.
Concentrations of pentobarbitone, ether, methoxyflurane, trichloroethylene and alphaxalone that are known to depress synaptic transmission in the prepiriform cortex also depressed the sensitivity of prepiriform neurones to l‐glutamate.
Halothane, in concentrations that depress synaptic transmission (< 1%) did not alter the sensitivity of neurones to glutamate. Higher concentrations (> 1%) produced a dose‐related depression of the glutamate sensitivity of neurones.
All four volatile anaesthetics tested caused some cells to alter their glutamate‐evoked firing pattern to one in which the spike discharges were more closely grouped. Pentobarbitone and alphaxalone had no such effect.
If the sensitivity of the neurones to the endogenous excitatory transmitter is affected by anaesthetics in the same way as the glutamate‐sensitivity, these results suggest that halothane depresses synaptic transmission by decreasing the amount of transmitter released from the nerve terminals, whereas the other anaesthetics depress the sensitivity of the post‐synaptic membrane to the released transmitter.
GENERAL ANAESTHETICS AND THE ACETYLCHOLINE‐SENSITIVITY OF CORTICAL NEURONES
Authors: SMAJE J.C. 
Published: July 2012

The effects of general anaesthetics on neuronal responses to iontophoretically‐applied acetylcholine have been examined in slices of guinea‐pig olfactory cortex maintained in vitro.
Acetylcholine excited 61% of the prepiriform neurones tested. The excitation was blocked by atropine, but not by dihydro‐β‐erythroidine or gallamine.
Alphaxalone reversibly depressed the acetylcholine‐sensitivity of prepiriform neurones. Pentobarbitone did not consistently depress the acetylcholine sensitivity of these cells.
Ether, methoxyflurane, trichloroethylene and halothane caused a dose‐related augmentation of acetylcholine‐induced firing.
These results show that general anaesthetics do not necessarily depress the sensitivity of nerve cells to all excitatory substances and that different anaesthetics may affect a particular excitatory process in various ways.
STRUCTURE‐ACTIVITY RELATIONS OF EXCITATORY AMINO ACIDS ON FROG AND RAT SPINAL NEURONES
Authors: BISCOE T.J. , EVANS R.H. , HEADLEY P.M. , MARTIN M.R. , WATKINS J.C. 
Published: July 2012

A series of compounds structurally related to glutamic acid has been tested on frog and rat spinal neurones. The substances were added to procaine‐containing medium bathing the isolated hemisected spinal cord of the frog, and their potencies in depolarizing motoneurones were assessed by the magnitude of the potential produced in the ventral root. The electrophoretic technique was used to administer the substances around single interneurones of the rat spinal cord and the relative potencies of the compounds as excitants assessed by the magnitude of the currents required to produce similar rates of neuronal firing.
Parallel structure‐activity relations were observed in the two series of experiments, suggesting that the receptors for excitatory amino acids on frog and rat spinal neurones are similar.
Quisqualate, domoate and kainate were the strongest excitants in both animals, with potencies around two orders of magnitude higher than that of l‐glutamate.
2,4,5‐Trihydroxyphenylalanine (6‐OH‐DOPA) was a stronger excitant and l‐3,4‐dihydroxyphenylalanine (l‐DOPA) a weaker excitant than l‐glutamate on frog spinal motoneurones. The former compound was also a more potent convulsant than l‐glutamate on intraventricular injection into mouse brain. The lack of activity of 6‐OH‐DOPA on electrophoretic administration was attributed to oxidation.
Unlike the majority of amino acid excitants, several of the compounds shown in the present work to have moderate excitatory activity are not anionic at physiological pH. This indicates either that two negatively charged groups are not essential for interaction with a common excitatory receptor, or that more than one type of receptor is involved in the actions demonstrated.
SLEEP INDUCED BY DRUGS INJECTED INTO THE INFERIOR HORN OF THE LATERAL CEREBRAL VENTRICLE IN DOGS
Authors: HARANATH P.S.R.K. , VENKATAKRISHNA‐BHATT H. 
Published: July 2012

1In unanaesthetized dogs, cholinomimetic drugs and their antagonists were injected into the inferior horn of the left lateral cerebral ventricle. Injection volumes of 5 μl were used to limit spread of the drugs beyond the inferior horn. The effects on EEG and behaviour were recorded and compared with the effects of the same doses given into the body of the right lateral ventricle a little behind the foramen of Monro.2Injections of cholinomimetic drugs into the inferior horn (acetylcholine 1‐2 μg, physostigmine 1.0 μg, pilocarpine 100 μg and nicotine 10 μg) induced sleep during the following hour. The same doses injected into the body of the lateral ventricle did not produce sleep.3Cholinolytic drugs (atropine 10‐20 μg, hyoscine 0.4‐1.6 μg, (±)‐tubocuraine 10‐20 ng and hexamethonium 40 μg) injected into the inferior horn also produced sleep, but the same doses injected into the body of the lateral ventricle were without effect. The EEG recorded after tubocurarine showed high voltage slow waves during sleep and desynchronized activation during rapid eye movement sleep.4Noradrenaline (10 μg) injected into the inferior horn produced sleep whereas the same dose given into the body of lateral ventricle did not produce sleep. The results with 5‐hydroxytryptamine were equivocal.5It is suggested that the site for induction of sleep lies in structures lining the inferior horn of the lateral cerebral ventricle and that the cholinomimetic drugs probably act by a depolarizing block and the acetlycholine antagonists by a competitive block.
NATURE OF HISTAMINE RECEPTORS CONCERNED IN CAPILLARY PERMEABILITY
Authors: BHARGAVA K.P. , NATH R. , PALIT G. 
Published: July 2012

1Histamine and 2‐methyl‐histamine (H1‐receptor agonist) caused dose‐dependent increases in capillary permeability in albino mice, but 4‐methyl‐histamine (H2‐receptor agonist) caused no significant increase.2Mepyramine (H1‐receptor antagonist) blocked the histamine‐induced increase in capillary permeability whereas burimamide (H2‐receptor antagonist) produced no significant blockade of the histamine‐response.3Combined mepyramine and burimamide pretreatment did not give any significantly greater protection than mepyramine alone.4The results indicate involvement of the H1‐receptors in histamine‐induced increase in capillary permeability.
KININ, KININOGEN AND KININASE LEVELS DURING ACUTE Babesia bovis (=B. argentina) INFECTION OF CATTLE
Authors: WRIGHT I.G. 
Published: July 2012

Kinin levels began rising on day 3 after infection of cattle with Babesia bovis (=B. argentina) and attained a maximum value of 98% above preinfection levels by day 7.
Kininogen levels began falling on day 3 and reached minimum levels of 83% below preinfection levels on day 8.
Changes in both kinin and kininogen levels on day 3 coincided with the detection of low levels of parasites, and with a fall in packed cell volume.
Plasma kininase levels rose significantly 6 to 9 days after infection. Preparations of lysed and sonicated uninfected and infected red cells contained kininase activity, the respective red cell preparations being 23.9 and 11.4 times more active per mg protein than uninfected red cell preparations. The effect of pH, and the inhibitors disodium edetate, 1,10 phenanthroline and aprotinin on normal and infected plasma and on the various red cell preparations suggested that the rise in plasma kininase levels during infection was probably at least partly due to parasite products.
These results are discussed in relation to previous data showing that both kallikrein activation and the onset of hypotension also occur on or about day 3.
THE ACTION OF MELATONIN ON SINGLE AMPHIBIAN PIGMENT CELLS IN TISSUE CULTURE
Authors: MESSENGER E. ANGELA , WARNER ANNE E. 
Published: July 2012

Neural crest material from neurula stage Xenopus embryos was tissue cultured as small aggregates of cells or a single cell suspension. Isolated pigment cells differentiated after 2 days in culture.
Melatonin (10−15 to 10−13 M) induced pigment granule condensation; it was 10,000 times more effective than any other compound tested.
Tests with appropriate agents showed the pigment cells to have β‐adrenoceptors and 5‐hydroxytryptamine receptors; these sites could be blocked without affecting the response to melatonin. Phentolamine blocked the effect of melatonin.
Removal of Na+ or Ca2+ from the bathing medium inhibited melatonin‐induced pigment granule condensation; 10 mM K+ induced pigment granule condensation. D600, Mn2+ and La3+, which inhibit Ca2+ entry, blocked the effect of melatonin.
Cyclic GMP induced pigment condensation and cyclic AMP pigment dispersion (10−2 to 10−4 M).
It is suggested that the action of melatonin is accompanied by depolarization and the entry of calcium ions.
Pigment cells in tissue culture could provide a useful bioassay method for melatonin.
COMPARATIVE EVALUATION OF THE in vitro EFFECTS OF HYDRALAZINE AND HYDRALAZINE ACETONIDE ON ARTERIAL SMOOTH MUSCLE
Authors: BARRON K. , CARRIER O. , HAEGELE K.D. , McLEAN A.J. , McNAY J.L. , DU SOUICH P. 
Published: July 2012

Dose‐response relationships to K+ were determined in isolated strips of rabit aorta.
K+ contractures were induced by 30 mM K+ in paired strips from individual animals. The effects of hydralazine and hydralazine acetone hydrazone (hydralazine acetonide) on these contractures were studied.
Hydralazine and hydralazine acetonide both produced dose‐dependent decreases of K+‐induced tone. Threshold concentrations for hydralazine were 11.89 ± 4.5 × 10−5 M (mean ± s.d.) and for hydralazine actonide 9.7 ± 4.6 × 10−5 M (0.5 < P < 0.4).
The magnitude of the effect of hydralazine acetonide was greater than that of hydralazine at all concentrations above threshold, as reflected in a significant difference (P < 0.05) in the slopes of dose‐response curves to the two treatments. The vasodilator effects of hydralazine and the acetonide were terminated by washout of the bath.
The differences in effect were not due to instability of hydralazine under in vitro conditions.
It is concluded that hydralazine acetonide has intrinsic activity on vascular smooth muscle which differs significantly from that of the parent compound and that this may contribute to the hypotensive effects which follow administration of the parent compound.
A CONFORMATIONAL ANALYSIS FOR LEUCINE‐ENKEPHALIN USING ACTIVITY AND BINDING DATA OF SYNTHETIC ANALOGUES
Authors: BEDDELL C.R. , CLARK R.B. , LOWE L.A. , WILKINSON S. , CHANG K.‐J. , CUATRECASAS P. , MILLER R. 
Published: July 2012

Leucine‐enkephalin and some analogues were assayed for activity in vitro on the mouse vas deferens and for binding to opiate receptors from rat brain.
The experimental data were analysed in terms of the stringency for glycine, a D‐amino acid or an L‐amino acid at each position in the peptide.
The observed configurational specificity was compared with the stringency that would be predicted to occur if enkephalin adopted certain hydrogen‐bonded conformations at the receptor.
A small subset of the conformations examined was found to be compatible with the experimental data.
BRL 13776: A NOVEL ANTIHYPERTENSIVE AGENT WITH INTERESTING MONOAMINE DEPLETING PROPERTIES
Authors: MELROSE JOANNE , PALFREYMAN M.G. , POYSER R.H. , WHITING R.L. 
Published: July 2012

Oral doses of 10‐100 mg/kg of BRL 13776 lowered the blood pressure of both deoxycorticosterone acetate (DOCA)/NaCl‐treated hypertensive rats and untreated normotensive rats.
BRL 13776 (100 mg/kg, orally) also reduced the blood pressure of renal hypertensive cats (cellophane perinephritis model).
No tolerance developed to the blood‐pressure lowering action of BRL 13776 when an oral daily dose of 100 mg/kg was administered repeatedly for up to 15 days to hypertensive rats and cats.
The fall in blood pressure to BRL 13776 in rats was associated with a reduction of tissue catecholamines.
The catecholamine depletion occurred in all the peripheral tissues examined but in the brain was restricted to certain regions, these being the hind‐brain on single dosing and the hind‐brain, hypothalamus and mid‐brain on repeated dosing. Catecholamine levels in the cerebral hemispheres were not affected by either single or repeated doses of BRL 13776.
BRL 13776 caused some reduction of the 5‐hydroxytryptamine content of the heart but not of whole brain or any brain region.
Neither single doses (up to 900 mg/kg orally) nor repeated doses (100‐300 mg/kg orally) of BRL 13776 produced any significant behavioural effects in animals.
BRL 13776 is a new type of agent to display both antihypertensive and monoamine‐depleting properties. The reduction of noradrenaline in certain brain regions may be a cause of the antihypertensive response but depletion in the periphery could contribute in a major or minor way. The differential action on noradrenaline in the brain together with the lack of effect on 5‐hydroxytryptamine might also explain the apparent absence of behavioural effects.
CANNABIS, CATECHOLAMINES, RAPID EYE MOVEMENT SLEEP AND AGGRESSIVE BEHAVIOUR
Authors: CARLINI E.A. , LINDSEY C.J. , TUFIK S. 
Published: July 2012

Previous work from our laboratory has shown that cannabis induces aggressive behaviour in rats that have been deprived of rapid eye movement (REM) sleep. It was suggested that this effect was related to brain catecholamines, with dopamine playing an agonist role and noradrenaline an inhibitory one. The present paper describes new experiments dealing with this subject.
Previous REM sleep‐deprivation enhanced both Δ9‐tetrahydrocannabinol (THC)‐induced hypothermia and nomifensine effects on aggressive behaviour.
A marihuana extract decreased brain dopamine turnover in REM sleep‐deprived rats, an effect not observed in non‐deprived rats. Noradrenaline metabolism was not altered.
Fighting behaviour was elicited in REM sleep‐deprived rats treated with 4 different dopamine‐β‐hydroxylase inhibitors.
Apomorphine, nomifensine and Δ9‐THC administered to non‐deprived rats pretreated with bis(4‐methyl‐1‐homopiperanzinyl‐thiocarbonyl) disulphide (Fla‐63), induced fighting behaviour.
Nomifensine and apomorphine induced fighting in non‐deprived rats pretreated with Δ9‐THC.
Clonidine inhibited the fighting elicited in REM sleep‐deprived rats by either Δ9‐THC or Fla‐63 pretreatment.
The data are discussed in terms of the influence of REM sleep‐deprivation (or the stress associated with deprivation) on the response to dopaminergic drugs and cannabis. Taken together they emphasize the participation of brain dopamine and noradrenaline systems in the aggressive behaviour studied.
CIRCULATORY EFFECTS OF PROSTAGLANDIN ENDOPEROXIDE ANALOGUES STUDIED IN THE DOG DURING LEFT VENTRICULAR BYPASS
Authors: ALTER I. , KOT P.A. , RAMWELL P.W. , ROSE J.C. , SHNIDER M.R. 
Published: July 2012

Intravenous administration of both the 9α,11α‐(epoxymethano) and 11α,9α‐(epoxymethano) analogues of prostaglandin H2 (0.25 üg/kg) produced a prominent rise in pulmonary arterial pressure and a moderate increase in systemic arterial pressure.
Direct administration of the endoperoxide analogues (1.25 μg/kg) into the bypass reservoir produced a greater rise in systemic arterial pressure and less prominent rise in pulmonary arterial pressure.
An intravenous dose of prostaglandin F2α that was 20 times larger was needed to produce a comparable rise in pulmonary arterial pressure.
The pulmonary and systemic pressor responses produced by the endoperoxide analogues were due to a direct increase in the vascular resistance.
HYPOTHALAMIC ADRENALINE SYNTHESIS AFTER STIMULATION OF THE MEDIAL FOREBRAIN BUNDLE
Authors: TORDA CLARA 
Published: July 2012

The problem of whether locally released noradrenaline can be methylated to adrenaline in the hypothalamus has been investigated.
During stimulation of the medial forebrain bundle (MFB) the hypothalamic adrenaline content increased somewhat, but the increase was not statistically significant (13%, mean of 10 experiments).
After inhibition of the activity of monoamine oxidase and catechol‐ O‐methyltransferase this increase was much larger (80%, mean of 9 experiments).
Adrenalectomy did not prevent the rise in hypothalamic adrenaline after stimulation of the MFB. These results suggest that noradrenaline released during activity of noradrenergic hypothalamic structures may be methylated to adrenaline in the hypothalamus.
SOME EFFECTS OF INTRAVENOUS PROSTAGLANDIN E1 AND ENDOTOXIN IN YOUNG CHICKENS
Authors: ARTUNKAL AKGÜL A. , MARLEY E. , STEPHENSON J. D. 
Published: July 2012

The effects of intravenous prostaglandin E1 and endotoxin were studied in young chickens (11–17 days old).
At a thermoneutral ambient temperature (31°C), intravenous prostaglandin E1 produced behavioural and electrocortical sleep, increased oxygen consumption and, after an initial fall, elevated body temperature. Below thermoneutrality (16°C), the initial hypothermic effect was more marked and oxygen consumption was lowered.
The soporific actions of prostaglandin E1 were sufficient to counteract dexamphetamine‐induced behavioural and electrocortical arousal and vocalization.
Intravenous injection of the O‐somatic antigen of Shigella dysenteriae evoked, after a latent period, long lasting hyperthermia. This indicates that in young chicks the blood brain barrier is probably permeable to endotoxins.
CHARACTERIZATION OF THE ADRENOCEPTOR IN THE ISOLATED CREMASTER MUSCLE OF THE GUINEA‐PIG
Authors: GUPTA R.S. , KELKAR V.V. 
Published: July 2012

Contractions of the isolated cremaster muscle of the guinea‐pig obtained in response to direct electrical stimulation were augmented by salbutamol, isoprenaline, adrenaline, noradrenaline and orciprenaline (in that order of potency), and by potassium chloride. Phenylephrine and xylometazoline had no effect.
The augmenting effect of isoprenaline on the twitch response was not altered by yohimbine or tolazoline, but was totally prevented by butoxamine, (‐) −1− (4‐nitrophenyl)‐2‐isopropylaminoethanol (INPEA), (±) ‐INPEA, sotalol, metalol and practolol; (+) ‐INPEA was much less effective. The augmenting effect of potassium was not altered by β‐adrenoceptor blockade.
The results are consistent with the view that the augmenting effect of the sympathomimetic agents is mediated through β2‐type of adrenoceptor in the skeletal muscle fibres.