bluuebunny/crossref_metadata_2025_split huggingface dataset:
INHIBITION OF NEURONAL FIRING BY OPIATES: EVIDENCE AGAINST THE INVOLVEMENT OF CYCLIC NUCLEOTIDES
Authors: KARRAS P.J. , NORTH R.A. 
Published: July 2012

Extracellular recordings were made in vitro from single neurones of the myenteric plexus of the guinea‐pig ileum.
Neuronal firing was inhibited by morphine and normorphine (10 nM to 1 μm). Cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) (100 μm to 1 mm) also inhibited the firing of the majority of the neurones. Prostaglandin E2 usually caused a short‐lasting excitation of myenteric neurones and the phosphodiesterase inhibitor 3‐isobutyl‐l‐methylxanthine was usually without effect on firing rate.
The inhibition of neuronal firing by normorphine was unaffected by prior and/or concurrent administration of cyclic AMP, dibutyryl cyclic adenosine 3′,5′‐monophosphate, prostaglandin E2 or 3‐isobutyl‐l‐methylxanthine. As these four treatments might be expected to elevate intracellular levels of cyclic AMP, the results lend no support to the notion that a reduction in intracellular cyclic AMP is essential to the inhibition of firing produced by morphine.
INVESTIGATION OF THE ROLE OF CALCIUM IN THE SUPER‐SENSITIVITYPRODUCED BY COCAINE IN CAT SPLEEN STRIPS
Authors: SUMMERS R.J. , TILLMAN JANET 
Published: July 2012

Cocaine (2 × 10−6m and 10−5m) produced 2 and 7 fold shifts to the left of the dose‐response curve to (—)‐noradrenaline recorded isotonically in isolated splenic capsular strips of the cat.
The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control.
Desmethylimipramine (DMI, 10 −7 to 10−6m) produced no significant potentiation of the response of cat spleen strips to (—)‐noradrenaline. At 10−5 M DMI decreased the maximum response.
Cocaine (10−5m) produced a 3.3 fold shift to the left of the dose‐response curve whereas DMI (10−6m) had no effect on the dose‐response curve to oxymetazoline in cat splenic capsular strips.
Cocaine (10−5m) in the presence of phentolamine (10−6m) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux.
Cocaine (10−5m) had no effect on the dose‐response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites.
The potentiating effect of cocaine (10−5m) on responses of spleen strips to (—)‐noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 × 10−5m).
It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.
EVIDENCE FOR DOPAMINERGIC VASODILATOR INNERVATION OF THE CANINE PAW PAD
Authors: BELL CHRISTOPHER , LANG WILLIAM J. 
Published: July 2012

In chloralose‐anaesthetized dogs pretreated with guanethidine and pancuronium, electrical stimulation (0.2 to 5 Hz) of the peripheral end of the cut tibial nerve caused a frequency‐dependent increase in femoral blood flow which was restricted to the paw pads.
This neurogenic vasodilatation was not attenuated by atropine, mepyramine plus burimamide, indomethacin or propranolol. It was, however, attenuated in a dose‐dependent manner by intra‐arterial administration of the dopamine receptor antagonist, ergometrine (0.05 to 0.5 mg).
The effect of ergometrine could not be explained by non‐specific effects on axonal conduction or transmission or by vasospasm of the blood vessels of the paw‐pads.
In dogs with intact tibial nerves, a pharmacologically similar dilator response localized to the paw‐pads could be elicited by electrical stimulation of loci in the ipsilateral diencephalon and midbrain. This response was not due to inhibition of adrenergic vasomotor tone and was abolished by systemic ganglion blockade or by tibial nerve section as well as by femoral arterial administration of ergometrine.
It is suggested that the vasculature of the canine paw pads is innervated by a population of autonomic axons which utilize dopamine or a related substance as a transmitter substance and activation of which causes vasodilation.
DOPAMINE AGONISTS AND COBALT‐INDUCED EPILEPSY IN THE RAT
Authors: FARJO I.B. , McQUEEN JUDITH K. 
Published: July 2012

Electrocorticogram (ECoG) recordings were made from conscious rats which had cortical implants of cobalt. The epileptiform spike activity was then assessed by means of an automated technique, based on peak angle measurements.
Apomorphine (0.5, 1.0 and 2.0 mg/kg i.p.) and lisuride (0.1, 0.25, 0.5 and 1.0 mg/kg i.p.) inhibited spike activity in established primary and secondary foci in a dose‐dependent manner. Bromocryptine (10 and 20 mg/kg i.p.) and CF 25–397 (40 mg/kg i.p.) had a similar effect but only after a latent period of several hours. Chronic administration of bromocryptine (20 mg/kg i.p. daily) attenuated the normal development of the foci following implantation.
Pimozide (1 mg/kg i.p.) potentiated cortical epileptic activity in cobalt‐implanted rats and blocked the antiepileptic effects induced by the dopamine agonists.
Intrastriatal administration of dopamine (25 μg) or apomorphine (60 μg) suppressed epileptiform spikes in the cortex. Destruction of striatal catecholamine terminals by 6‐hydroxydopamine increased the spike activity.
It is concluded that the striatum may play an essential part in mediating the anti‐epileptic effects of dopamine and its agonists in this model of epilepsy.
THE SUBDIVISION OF β‐ADRENOCEPTORS IN THE CARDIOVASCULAR SYSTEM OF THE RAT
Authors: IMMS F.J. , NEAME R.L.B. , POWIS D.A. 
Published: July 2012

The antagonism by the β‐adrenoceptor blocking drugs, propranolol (non‐selective) and practolol (β‐selective), of the cardiovascular actions of isoprenaline has been investigated in the rat.
All doses of practolol (0.1, 1 and 3 mg/kg) blocked the cardio‐accelerator action of isoprenaline but only the largest dose blocked the vasodilator effect.
All doses of propranolol (0.01, 0.03 and 0.1 mg/kg) blocked the vasodilator effect of isoprenaline but only the largest dose diminished the tachycardia.
It is concluded that in the rat, as in other species, β‐adrenoceptors may be subdivided into β1 (cardiac) and β2 (peripheral vascular) types.
THE EFFECTS OF IONS ON THE BINDING OF AGONISTS AND ANTAGONISTS TO MUSCARINIC RECEPTORS
Authors: BIRDSALL N.J.M. , BURGEN A.S.V. , HULME E.C. , WELLS J.W. 
Published: July 2012

There are no selective effects of Na+, K+, Ca2+, Mg2+ or Cl− on the binding of antagonists or agonists to muscarinic receptors in rat brain. A decrease in affinity related to ionic strength is found for all these ions.
Larger effects were produced by T+, La3+, and some transition metal ions.
NALOXONE INHIBITS THE ANTI‐DIARRHOEAL ACTIVITY OF LOPERAMIDE
Authors: PIERCEY M.F. , RUWART M.J. 
Published: July 2012

Subcutaneous prostaglandin E2 (2.5 mg/kg) produces profuse diarrhoea in fed rats.
Pretreatment of rats with subcutaneous loperamide (1.0 mg/kg) completely prevents prostaglandin‐induced diarrhoea. If naloxone is administered prior to loperamide injections the activity. of the antidiarrhoeal compound is completely destroyed.
These data provide strong evidence that the antidiarrhoeal activity of loperamide is mediated via the opiate receptor.
INVOLVEMENT OF SRS‐A IN THE SCHULTZ‐DALE RESPONSE OF THE GUINEA‐PIG SMALL INTESTINE
Authors: HERMAN A.G. , LAEKEMAN G.M. , VAN BEEK H.A. 
Published: July 2012

The anaphylactic reaction of the guinea‐pig ileum, the so called Schultz‐Dale reaction, shows a biphasic response: a short rapid contraction followed by a partial relaxation and a slow contractile response.
Dose‐response curves with ovalbumin as an antigen were obtained for the quick and slow contraction of this anaphylactic reaction.
Mepyramine (1 μg/ml) blocked the rapid first contraction, but failed to abolish the slow one in about 50% of the animals studied.
The SRS‐A antagonist, FPL 55712, significantly depressed the slow sustained contraction during the Schultz‐Dale reaction. Disodiumcromoglycate was without effect on both phases when it was added 5 min before addition of the antigen. However, when added simultaneously with the antigen it produced a 30% suppression of the slow phase in the highest concentration used.
5‐HYDROXYTRYPTAMINE UPTAKE INHIBITORS BLOCK para‐METHOXYAMPHETAMINE‐INDUCED 5‐HT RELEASE
Authors: TSENG LIANG‐FU 
Published: July 2012

Activation of myoclonic twitch activity (MTA) of suprahyoideal muscle after p‐methoxyamphetamine (PMA) administration in rats anaesthetized with urethane has previously been reported to be due to brain 5‐hydroxytryptamine (5‐HT) release. Increased MTA caused by PMA was blocked by chlorimipramine (0.1 to 1 mg/kg) and fluoxetine (0.3 to 3 mg/kg) but not by desipramine (3 mg/kg).
The 5‐hydroxytryptophan‐induced increase of MTA of suprahyoideal muscle in rats pretreated with pargyline was not blocked by chlorimipramine but was blocked by methysergide.
[3H]‐5‐HT was injected intraventricularly 30 min before the beginning of ventricular perfusion with artificial cerebrospinal fluid in urethane anaesthetized rats. PMA (2 mg/kg i.v.) increased the release of [3H]‐5‐HT in the perfusate after injection. Chlorimipramine (0.1 to 1 mg/kg) and fluoxetine (0.1 to 1 mg/kg), injected 10 min before the PMA injection, caused a dose‐related blockade of the increased release of [3H]‐5‐HT induced by PMA. Desipramine at 3 mg/kg slightly inhibited the increased release of [3H]‐5‐HT caused by PMA but was inactive at 1 mg/kg.
It is proposed that these 5‐HT uptake inhibitors block the increased MTA caused by PMA by preventing the PMA‐induced release of 5‐HT in the central nervous system.
CHARACTERIZATION OF ULTRAVIOLET LIGHT‐INDUCED RELAXATION OF THE ISOLATED DUODENUM OF THE RAT
Authors: DAVE K.C. , JINDAL M.N. , KELKAR V.V. , TRIVEDI H.D. 
Published: July 2012

Isolated duodenum of the rat, exposed to ultraviolet (u.v.) light in the presence of NO2 ions, responded with reversible relaxation.
The photorelaxation response did not seem to involve any known receptor mechanisms and was independent of any ganglionic or neuronal influences.
Changes in the ionic environment of the tissue showed that Na+ and Ca2+ were essential for the photorelaxation. K+ depolarized‐tissue did not show the photoresponse.
The presence of the metabolic inhibitors, iodoacetic acid, 2,4‐dinitrophenol, sodium fluoride, sodium azide or potassium cyanide, abolished the photorelaxation response.
It is proposed that the photorelaxation of the tissue resulted from the liberation of metabolic energy following NO2 ion‐dependent absorption of u.v. light energy, which in turn, interfered with the Na+ ion movement across the cell membrane.
AN ANALYSIS OF THE NEGATIVE INOTROPIC ACTION OF SOMATOSTATIN
Authors: QUIRION R. , REGOLI D. , RIOUX F. , ST‐PIERRE S. 
Published: July 2012

Somatostatin (SS) was evaluated as a chronotropic and inotropic agent in isolated spontaneously beating auricles of rats, rabbits and guinea‐pigs.
SS was completely inactive in rat and rabbit auricles but exerted a dose‐dependent, negative inotropic effect in guinea‐pig auricles in concentrations between 1.5 × 10−8 to 1.2 × 10−6 m.
The negative inotropic effect of SS (6.0 × 10−8 and 3.0 × 10−7 m) was not inhibited by a mixture of antagonists containing practolol (7.9 × 10−6 m), phentolamine (3.5 × 10−7 m), methysergide (2.8 × 10−7 m), diphenhydramine (3.9 × 10−5 m), cimetidine (4.0 × 10−5 m) atropine (3.4 × 10−7 m) and indomethacin (1.4 × 10−5 m).
The negative inotropic effect of SS was greatly potentiated by reduction in the Ca2+ concentration of the medium from 5.0 to 1.25 mm.
On a molar basis, SS was equipotent with acetylcholine (ACh) as a negative inotropic agent in the guinea‐pig auricles.
SS (6.0 × 10−8 and 6.0 × 10−7 m) was found to inhibit selectively the positive inotropic action of neurotensin (NT) in guinea‐pig but not in rat auricles.
The inhibitory action of SS against NT was independent of its negative inotropic action.
These results suggest that SS produces its negative inotropic action by interacting with specific receptors presumably located in the cell membrane of guinea‐pig atria. The interaction between SS and its receptor may cause a decreased Ca2+ diffusion and/or transport into the atrial cells. The physiological and pharmacological significance of these results is discussed.
RAPID ABSORPTION FROM THE URINARY BLADDER OF A SERIES OF n‐ALKYL CARBAMATES: A ROUTE FOR THE RECIRCULATION OF DRUGS
Authors: BRIDGES J.W. , SARGENT N.S.E. , UPSHALL D.G. 
Published: July 2012

The rate of loss of a series of n‐alkyl carbamates from the lumen of the urinary bladders of female rats has been studied.
The rate of loss obeys first order kinetics and was not affected by water flux across the bladder wall nor by binding of the carbamates to it.
The rate of loss of octyl carbamate was reduced by about 76% by the presence of 5% Tween 80. Histological evidence indicates that this may be due to the formation of a thin luminal lining which may be adsorbed Tween 80 or mucopolysaccharide material.
The absorption rate of the carbamates was limited by their hydrophilicity but reached a plateau for the more lipophilic homologues with a half life for loss of approximately 10 min.
The implications of these results with regard to the recirculation of unmetabolized drugs and hydrolysed conjugates of drugs, the systemic absorption of intravesically applied cancer chemotherapeutic agents and bladder wall permeability to carcinogens are discussed.
THE EFFECT OF POTASSIUM ON FROG STOMACH MUSCLE
Authors: BAYSAL F. , ÖNDER S. , ÖZGÜL M. , TOYGAR A. 
Published: July 2012

KCl relaxed strips of frog stomach muscle. Usually, the effect was biphasic, i.e. contraction followed by relaxation at a concentration of 137 mm.
The effect was mimicked by K2SO4.
Ouabain (5 and 10 μg/ml) blocked the relaxations and reversed them to contractions. The tension of strips was not affected.
Phenoxybenzamine (1 μg/ml) and procaine (20 μg/ml) inhibited the relaxations, potentiated the contractile component and lowered the tone of the muscle.
The relaxation and the tone were inhibited by papaverine (5 μg/ml) but the contractile component was unaffected.
It is suggested that potassium‐induced relaxations are mediated through the activation of the sodium pump.
RELAXANT RESPONSE OF GOAT TRACHEA TO 5‐HYDROXYTRYPTAMINE MEDIATED BY D‐TRYPTAMINE RECEPTORS
Authors: CHAND N. , DeROTH L. , EYRE P. 
Published: July 2012

Goat isolated trachea contracted in response to carbachol, histamine and 2‐pyridylethylamine (an H1‐receptor agonist) and relaxed after application of isoprenaline, 5‐hydroxytryptamine (5‐HT) and phenylephrine.
Mepyramine, a selective H1‐receptor antagonist, blocked histamine‐ and 2‐pyridylethylamine‐induced contractions. In high doses it also exhibited some nonspecific antagonism to carbachol. After H1‐receptor blockade, 4‐methylhistamine and dimaprit (specific H2‐agonists) relaxed the carbachol‐contracted trachea.
Propranolol, a β‐adrenoceptor blocker, antagonized relaxation in response to isoprenaline and phenylephrine. In high doses, it produced a reversal of the phenylephrine response.
Indomethacin enhanced contractions in response to carbachol and histamine.
Relaxation to 5‐HT was not affected by propranolol, indomethacin, metiamide or cimetidine (H2‐blockers). These findings appear to exclude the involvement of adrenergic, prostaglandinergic and H2‐histaminergic mechanisms in the mediation of this response.
Atropine potentiated 5‐HT‐induced relaxations. This suggests the participation of a ‘masked’ excitatory cholinergic mechanism.
Methysergide, dibenamine and dibenzyline selectively antagonized or reversed 5‐HT‐induced relaxation. Dibenamine and dibenzyline enhanced relaxations to isoprenaline.
This investigation showed (i) a relaxant response of goat trachea to 5‐HT, mediated via D‐muscular tryptamine receptors; (ii) a small population of excitatory M‐neuronal tryptamine and α‐adrenoceptors; and (iii) predominance of H1‐histamine receptors in the goat trachea.
CHARACTERIZATION OF VASCULAR HISTAMINE RECEPTORS IN THE RAT
Authors: POWELL JAMES R. , SHAMEL L. BLAIR 
Published: July 2012

In the rat the decrease in blood pressure caused by histamine involves activation of both H1‐ and H2‐receptors. Since arterial pressure measurements alone do not permit the separation of responses into cardiac and vascular components, the following experiments were undertaken to study vascular histamine receptors.
Vascular responses were studied in the autoperfused hindquarters of anaesthetized rats. Intra‐arterial histamine caused vasodilatation which was only partially attenuated by treatment with mepyramine, an H1‐receptor antagonist. Treatment with metiamide, the H2‐receptor antagonist, did not affect vasodilatation caused by histamine but did attenuate vasodilatation which persisted after mepyramine.
Intra‐arterial 4‐methylhistamine, an H2‐receptor agonist, caused vasodilatation which was reduced by metiamide. The H1‐receptor agonist, 2‐(2‐pyridyl)ethylamine also caused vasodilatation which was blocked by mepyramine.
It is concluded that in the rat, histamine causes vasodilatation mediated by both H1‐ and H2‐receptors.
THE RELEASE OF PROSTAGLANDIN E2 FROM THE SKIN OF THE PLAICE, Pleuronectes platessa L.
Authors: ANDERSON A.A. , FLETCHER THELMA C. , SMITH G.M. 
Published: July 2012

A fungal extract which produces a cutaneous hypersensitivity reaction in the plaice, Pleuronectes platessa L., was incubated in vitro with the skin of this teleost fish. Samples of incubation media were assayed for smooth muscle stimulating activity.
Prostaglandin E2 was identified by bioassay, thin‐layer chromatography, ultraviolet absorption spectroscopy and gas chromatography‐mass spectrometry. Release from challenged skin was maximum after 60 min incubation.
Analysis of the fatty acid composition of plaice skin showed that although arachidonic acid was present (3% of total fatty acids), the precursor of prostaglandin E3, eicosapentaenoic acid contributed 9% of total.
Indomethacin (50 mg/kg i.p.) did not inhibit the erythema induced by the fungal extract, whilst a dose of 1 mg/kg maximally inhibited prostaglandin release from skin on incubation in vitro.
It is concluded that prostaglandins do not have an exclusive role in the mediation of the hypersensitivity reaction.
BACKWARD WALKING AND CIRCLING: BEHAVIOURAL RESPONSES INDUCED BY DRUG TREATMENTS WHICH CAUSE SIMULTANEOUS RELEASE OF CATECHOLAMINES AND 5‐HYDROXYTRYPTAMINE
Authors: CURZON G. , FERNANDO J.C.R. , LEES A.J. 
Published: July 2012

The roles of catecholamine and 5‐hydroxytryptamine (5‐HT) release in mediating backward walking and circling were studied in rats.
These behaviours occurred in animals given 15mg/kg intraperitoneally of (+)‐amphetamine (which predominantly releases catecholamines) or either p‐chloroamphetamine or fenfluramine (which predominantly release 5‐HT). They also occurred when smaller doses of (+)‐amphetamine (5mg/kg) and either p‐chloroamphetamine (2–5 mg/kg) or fenfluramine (5 mg/kg) were given together.
Characteristic dopamine‐dependent behaviours (rearing, licking, gnawing) resulting from (+)‐amphetamine injection were greatly reduced by p‐chloroamphetamine or fenfluramine.
Characteristic 5‐HT‐dependent behaviours (wet dog shake, hind limb abduction) resulting from injection of either p‐chloroamphetamine or fenfluramine were unaffected by (+)‐amphetamine.
Fragmentary backward walking and circling resulting from levallorphan injection (50 mg/kg s.c.) were decreased by (+)‐amphetamine at low dosage.
Results in general strengthen previous evidence that backward walking and circling are mediated by simultaneous dopamine and 5‐HT release.
The possible relevance of the above findings to hallucinogenic activity, amphetamine psychosis, schizophrenia and abnormal movements due to l‐DOPA treatment is discussed.
THE INHIBITORY EFFECTS OF PRESYNAPTIC α‐ADRENOCEPTOR AGONISTS ON CONTRACTIONS OF GUINEA‐PIG ILEUM AND MOUSE VAS DEFERENS IN THE MORPHINE‐DEPENDENT AND WITHDRAWN STATES PRODUCED in vitro
Authors: GILLAN MAUREEN G.C. , KOSTERLITZ H.W. , ROBSON LINDA E. , WATERFIELD ANGELA A. 
Published: July 2012

Isolated ilea from guinea‐pigs implanted with morphine pellets were stimulated coaxially, either with or without morphine present in the bath fluid, and the longitudinal contractions recorded.
In the absence of morphine the inhibitory effects of the presynaptic α‐adrenoceptor agonists, clonidine and oxymetazoline were much reduced and the dose‐response curve was flat. This state of ‘withdrawal’ was readily reversed by morphine and levorphanol but not its inactive (+)‐isomer, dextrorphan.
The κ‐agonists, ketazocine and ethylketazocine, also restored the effects of clonidine as did the opioid peptides Tyr‐d‐Ala‐Gly‐Phe‐d‐Leu, acting preferentially on δ‐receptors, and Tyr‐d‐Ala‐Gly‐MePhe‐Met(O)‐ol, acting mainly on μ‐receptors.
The inhibitory effects of adrenaline and adenosine 3′,5′‐diphosphate were reduced at low but not at high concentrations.
In contrast, the inhibitory effect of clonidine on the electrically evoked contractions of vasa deferentia from mice implanted with morphine pellets was not abolished by the lack of morphine in the bath fluid or by addition of naloxone.
A possible explanation is suggested for the loss of the inhibitory effects of presynaptic α‐adrenoceptor agonists in the withdrawn state of the dependent ileum.
ACETYLCHOLINE RECEPTORS IN THE CILIARY GANGLION AND IN THE IRIS MUSCLE OF THE CHICK: SPECIFIC BINDING AND EFFECT ON THE SYNAPTIC TRANSMISSION OF THE NEUROTOXIN FROM Naja naja siamensis
Authors: CONTI‐TRONCONI B. , GOTTI C. , PAGGI P. , ROSSI A. 
Published: July 2012

A specific binding of Naja naja siamensis neurotoxin was found both in the iris and in the ciliary ganglion of the chick.
Naja‐toxin (125 nm) caused a complete block of the iris muscle contraction induced by carbamyl‐choline.
Naja‐toxin had a different effect on the two neuronal populations present in the ganglion: it blocked the synaptically evoked response of the ciliary cells, while the response of the choroid ones was only slightly reduced. The effects were the same in a wide range of concentrations (125 to 2500 nm).
The results obtained in the iris show the existence of an acetylcholine receptor population similar to the nicotinic receptor of the skeletal muscle.
In the ciliary ganglion the results confirm the existence of different acetylcholine receptors on the two cell types.