bluuebunny/crossref_metadata_2025_split huggingface dataset:
HYPOTENSION PRODUCED BY INTRAVENOUS APOMORPHINE IN THE ANAESTHETIZED DOG IS NOT CENTRALLY MEDIATED
Authors: BOGAERT M.G. , BUYLAERT W.A. , WILLEMS J.L 
Published: July 2012

Intravenous administration of apomorphine (1.25 to 20 μg/kg) in the anaesthetized dog produced a dose‐dependent decrease in blood pressure which was antagonized by haloperidol but not influenced by propranolol or atropine.
Intracarotid administration of apomorphine produced a systemic hypotension which was significantly smaller than that seen with intravenous injection.
Doses of apomorphine that caused a decrease in blood pressure on intravenous injection, had no effect on blood pressure or caused retching accompanied by an increase in blood pressure on intravertebral or intracisternal administration. The animals showed a marked hypotension on intra‐vertebral or intracisternal injection of clonidine.
From these results it is concluded that the hypotension seen with intravenous apomorphine cannot be explained by a central site of action.
MECHANICAL RESPONSES OF THE ISOLATED CERVIX AND UTERINE HORN OF PREGNANT RATS NEAR TERM TO DRUGS
Authors: HOLLINGSWORTH M. , ISHERWOOD CATHERINE N. M. 
Published: July 2012

The responses of circularly cut strips of cervix and uterine horn from rats on days 20 and 22 of pregnancy to drugs were compared in vitro.
The cervix exhibited similar responses and sensitivities to acetylcholine, bradykinin, prostaglandin (PG) F2a (day 20) and isoprenaline (day 20) as did the uterine horn but was less sensitive or responded less consistently to isoprenaline (day 22), oxytocin and PGEj. PGE2 was more potent on the cervix (day 20).
Before term the relatively inextensible connective tissue of the cervix plus contractions of the smooth muscle would help to prevent foetal expulsion. At term the cervical smooth muscle is sufficiently unresponsive to allow cervical dilatation.
EFFECT OF CROTAMINE, A TOXIN OF SOUTH AMERICAN RATTLESNAKE VENOM, ON THE SODIUM CHANNEL OF MURINE SKELETAL MUSCLE
Authors: CHANG C. CHIUNG , TSENG K. HONG 
Published: July 2012

Crotamine (0.5 μg/ml) augmented the single twitch response of the rat and mouse isolated diaphragm to direct stimulation and prolonged the time course of contraction. At higher doses (10 to 50 μg/ml), contracture was observed with spontaneous fibrillation.
The resting membrane potential of diaphragm was rapidly depolarized to about −50 mV within 5 minutes. No increase of depolarization occurred on prolongation of the incubation time or increase of crotamine concentration from 0.5 μg/ml to 50 μg/ml. The effect was not reversed by washing.
Tetrodotoxin, low Na+ (12 mm), Ca2+ (10 mm) and procaine (1 mm) prevented the crotamine‐depolarization. However, depolarization resumed when crotamine and the antagonists were removed.
Low Cl− (8.5 mm) and pretreatment with ouabain enhanced depolarization by crotamine.
High K+ (25 to 50 mm) prevented the further depolarization by crotamine and the membrane potential was restored to normal on washout of crotamine with normal Tyrode solution.
Effective membrane resistance was decreased by about 50% by crotamine.
24Na‐influx of the rat diaphragm was increased by crotamine. 42K‐influx was slightly increased if tetrodotoxin was also present but was decreased in the absence of tetrodotoxin.
No effect on the miniature and evoked endplate potential of the rat diaphragm was observed. Skeletal muscles from frog and chick were not affected.
It is inferred that crotamine acts on a molecule regulating the Na+‐ permeability of the Na+ channel of murine muscles. It is proposed that extracellular K+ depresses the permeability of the Na+ channel by acting on the same regulator molecule.
COMPARISON OF THE ACTIONS OF OCTOPAMINE AND CATECHOLAMINES ON SINGLE NEURONES OF THE RAT CEREBRAL CORTEX
Authors: HICKS T.P. , McLENNAN H. 
Published: July 2012

The technique of microelectrophoresis was used to compare the actions of octopamine, noradrenaline and dopamine on single cortical neurones of the rat.
Octopamine both excited and depressed neurones of the cortex. Frequently cells depressed by noradrenaline were excited by octopamine; occasionally the converse was true. The time courses of action of the two amines also differed. Dopamine‐elicited excitations were observed, but also were not correlated with octopamine‐elicited effects.
When octopamine and noradrenaline both caused depressant effects, octopamine frequently was of less apparent potency than noradrenaline. When these amines were excitatory, octopamine appeared at least as and sometimes more potent than noradrenaline.
Octopamine was only weakly effective on cortical neurones identified by antidromic stimulation of the pyramidal tract, or synaptically excited by stimulation of the ventrobasal thalamus.
α‐Flupenthixol and propranolol were without effect on octopamine‐elicited changes in firing rate at doses which were effective in blocking the actions of dopamine and noradrenaline respectively. Metoclopramide did not block the actions of any of the three agonists, but had strong effects of its own.
The results suggest that receptors sensitive to octopamine, and which appear to be pharmacologically distinct from those previously categorized as noradrenaline and dopamine receptors, may exist on central neurones of the rat.
A PHARMACOLOGICAL INVESTIGATION OF THE ELECTRICALLY EVOKED CONVULSIVE ACTIVITY INDUCED BY ADMINISTRATION OF CATECHOL IN THE ANAESTHETIZED RAT
Authors: ANGEL A. , DEWHURST D.G. 
Published: July 2012

The response evoked by electrical stimulation at the wrist has been recorded from muscles of the forelimb of anaesthetized rats induced to convulse by administration of catechol.
This response can be divided into three temporally distinct components, the characteristics of which have been described.
The probability of occurrence of the two early components of the response has been measured before and after administration of various drugs. The results show that the first component is not affected by cholinoceptor or adrenoceptor blocking drugs or anticholinesterase agents. The probability of occurrence of the second component is significantly reduced by cholinoceptor blocking drugs and increased by physostigmine.
The implications of these results in explaining the convulsant actions of catechol are discussed.
FACTORS INFLUENCING THE RELEASE OF ACETYLCHOLINE FROM THE MYENTERIC PLEXUS OF THE ILEUM OF THE GUINEA‐PIG AND RABBIT
Authors: COWIE A. LOUISE , KOSTERLITZ H.W. , WATERFIELD ANGELA A. 
Published: July 2012

The effects of electrical stimulation, changes in external ion concentrations and various drugs on acetylcholine release from the myenteric plexus were measured by bioassay in the presence of physostigmine and by recording the responses of the longitudinal muscle. In preparations from the guinea‐pig, the acetylcholine output per pulse increased with decreasing frequency of stimulation and reached its maximum at a frequency of 0.017 Hz (1/min) and thus ensured that the output per unit of time was constant at frequencies below 0.5 Hz. Spontaneous release was suppressed during stimulation at 0.017 Hz.
In the rabbit, the fractional acetylcholine release was lower than in the guinea‐pig. The output per pulse increased with decreasing frequency of stimulation but at a lesser rate, with the effect that the output per unit time decreased between 0.5 and 0.017 Hz.
In the guinea‐pig, reduction of the Ca2+ concentration, addition to the bath fluid of Mn2+, ganglion‐blocking drugs, morphine and catecholamines reduced output more at low than at high frequencies of stimulation. In the rabbit, acetylcholine output was less sensitive to changes in Ca2+ concentration and insensitive to Mn2+ and morphine.
In the guinea‐pig, morphine and catecholamines depressed both the contractile response and acetylcholine output whereas Mn2+ in concentrations up to 125 μm, bretylium and ganglion‐blocking drugs depressed only acetylcholine output.
In preparations from the guinea‐pig, drugs blocking noradrenergic neurones or α‐adrenoceptors, e.g. bretylium, phenoxybenzamine, thymoxamine and phentolamine, increased acetylcholine output during stimulation at high (1.5 to 10 Hz) but not at low frequencies.
The implications of these findings for the release of acetylcholine from different pools in the heterogeneous myenteric plexus are considered. The possible errors, introduced by the effects of physostigmine, on the size of the acetylcholine pools and on the transmission of impulses within the myenteric plexus are discussed.
COMPARISON OF THE RECEPTOR BINDING CHARACTERISTICS OF OPIATE AGONISTS INTERACTING WITH μ‐ OR K‐RECEPTORS
Authors: KOSTERLITZMM H.W. , LESLIE FRANCES M. 
Published: July 2012

The receptor binding characteristics of various morphine‐like and ketazocine‐like opiate agonists were measured by inhibition of [3H]‐naloxone binding in homogenates of brain and of ileal myenteric plexus‐longitudinal muscle of the guinea‐pig. No differences were found for the two tissues.
The depressant effect of Na+ on the inhibition of [3H]‐naloxone binding by opiate agonists varies widely, giving sodium shifts between 5 and 140. The relationship between Na+ concentration and inhibition of binding is non‐linear, the magnitude of the sodium shift varying directly with the slope of the regression of log IC50 on log [NaCl].
The sodium shift of ketazocine‐like agonists is lower than that of morphine‐like agonists but higher than that of opiates with dual agonist and antagonist action. A working hypothesis is proposed which suggests that the /c‐receptors for the ketazocine‐like drugs are less susceptible to the Na+ effect than the u‐receptors for the morphine‐like drugs.
For most of the morphine‐like but not the ketazocine‐like agonists, a good correlation has been found for the pharmacological activity in the myenteric plexus‐longitudinal muscle preparation and the inhibition of binding of [3H]‐naloxone at 12 mm Na+. An exception is fentanyl which has a much greater pharmacological potency than may be expected from its potency in inhibiting [3H]‐naloxone binding.
RELEASE OF [3H]‐N0RADRENALINE FROM THE MOTOR ADRENERGIC NERVES OF THE ANOCOCCYGEUS MUSCLE BY LYSERGIC ACID DIETHYLAMIDE, TYRAMINE OR NERVE STIMULATION
Authors: McGRATH J.C. , OLVERMAN H.J. 
Published: July 2012

A method is described for labelling the neuronal noradrenaline (NA) stores of rat anococcygeus with [3H]‐NA and detecting subsequent release of 3H from the superfused tissue by nerve stimulation or drugs.
Lysergic acid diethylamide (LSD) or tyramine but not barium chloride or carbachol increased the efflux of 3H although each drug produced an equivalent contractile response. This confirms that LSD has an indirect sympathomimetic action.
LSD was found to produce a proportionately smaller reduction of the nerve‐induced efflux of 3H than of the accompanying contractile response.
The inhibition of nerve‐induced contractile responses by LSD was shown to be independent of the neuronal uptake of noradrenaline and any post‐junctional inhibition demonstrated to be non‐specific.
CORONARY ANAPHYLAXIS in vitro
Authors: CHAND N. , EYRE P. 
Published: July 2012

The reactivity of isolated coronary arteries and cardiac veins of the calf to selected chemical mediators of anaphylaxis and to sensitizing antigen (horse plasma) was studied.
Both the coronary arteries and cardiac veins contracted to bradykinin, 5‐hydroxytryptamine (5‐HT), prostaglandin E2 (PGE2), PGF2α, histamine and carbachol.
Isoprenaline and PGE1 relaxed vessels which had been partially contracted by PGF2α, PGE2, histamine, 5‐HT, bradykinin, carbachol or antigen.
Horse plasma (antigen) contracted coronary vessels obtained from sensitized calves, but not from control calves. Subsequent antigen ‘challenge’ produced ‘desensitization’ (tachyphylaxis). After 1 or 2 h of rest, the anaphylactic response partially recovered although there was no change in tissue reactivity to the exogenous agonists.
Specific doses of atropine, mepyramine (H1‐blocker) and methysergide (5‐HT antagonist) did not modify the anaphylactic reaction in coronary arteries, suggesting a negligible role for these biogenic amines.
Compound PRD‐92‐EA (a new anti‐allergic agent) exhibited non‐specific receptor blocking activity towards histamine, 5‐HT and carbachol and inhibited the coronary anaphylactic reaction.
THE INFLUENCE OF CEREBRAL 5‐HYDROXYTRYPTAMINE ON CATALEPSY INDUCED BY BRAIN‐AMINE DEPLETING NEUROLEPTICS OR BY CHOLINOMIMETICS
Authors: FUENMAYOR LUIS D. , VOGT MARTHE 
Published: July 2012

Catalepsy was produced in rats and mice by the subcutaneous injection of either tetrabenazine or the butyrophenone U‐32,802A (4′‐fluoro‐4‐{[4‐(p‐fluorophenyl)‐3‐cyclohexen‐1‐yl]amino} butyrophenone hydrochloride). Catalepsy was evaluated by the duration of total immobility on a vertical grid.
Pretreatment with p‐chlorophenylalanine (PCPA) reduced the intensity of catalepsy by 50% or more, whereas its time course remained the same.
5‐Hydroxytryptophan (5‐HTP), 10 mg/kg, enhanced the catalepsy induced by U‐32,802A or tetrabenazine, provided it was administered soon (45 min) after the neuroleptic; injections at 90 min had no effect. Otherwise untreated rats given this dose of 5‐HTP behaved normally on the grid.
The anticataleptic effect of PCPA was reversed by 5‐HTP.
Measurable changes in 5‐hydroxytryptamine (5‐HT) metabolism in the rat forebrain accompanied the modification of catalepsy by 5‐HTP and PCPA.
Methysergide (5 mg/kg) given 30 min before the neuroleptics to either mice or rats reduced the catalepsy, assessed 2.5 h after the methysergide. It also prevented the increase in neuroleptic‐induced catalepsy following 5‐HTP, 10 mg/kg.
Tryptophan, like 5‐HTP, increased the catalepsy seen in mice after U‐32,802A and tetrabenazine, and increased the production of 5‐hydroxyindol‐3‐ylacetic acid in the forebrain.
In the rat, intracerebroventricular injection of physostigmine produced catalepsy which was not modified by methysergide or PCPA but was abolished by atropine. Similarly, in the mouse, catalepsy induced by the subcutaneous injection of pilocarpine was abolished by atropine but not affected by either methysergide or 5‐HTP.
Atropine greatly reduced the catalepsy induced by U‐32,802A and tetrabenazine but lowered striatal homovanillic acid (HVA) only after U‐32,802A. d, l‐DOPA, 20 mg/kg, diminished the cataleptogenic effect of both neuroleptics and raised striatal HVA.
The results support the view that there is a facilitating or permissive action of 5‐HT‐containing neurones on neuroleptic‐induced catalepsy.
EFFECTS OF THE HISTAMINE H2‐RECEPTOR BLOCKING DRUGS BURIMAMIDE AND CIMETIDINE ON NORADRENERGIC TRANSMISSION IN THE ISOLATED AORTA OF THE RABBIT AND ATRIA OF THE GUINEA‐PIG
Authors: McCULLOCH M.W. , MEDGETT I.C. , RAND M.J. 
Published: July 2012

In rabbit aortic strips, concentration‐response curves to noradrenaline (NA) were shifted to the right in a parallel and concentration‐dependent manner by the α‐adrenoceptor blocking drug, phentolamine and also by the histamine H2‐receptor blocking drugs, burimamide and cimetidine. Responses to 5‐hydroxytryptamine were not affected by these drugs.
Burimamide had the properties of a competitive antagonist of noradrenaline, possessing about one‐hundredth the potency of phentolamine. Cimetidine was weaker than burimamide and did not fulfil the requirements for competitive antagonism of noradrenaline.
In guinea‐pig isolated atria, in which noradrenergic transmitter stores were labelled with [3H]‐noradrenaline, phentolamine (3 μm), burimamide (30 μm) and cimetidine (30 μm), in decreasing order of effectiveness, each enhanced stimulation‐induced efflux of [3H]‐noradrenaline, indicating that their blocking effects on prejunctional α‐adrenoceptors in this tissue are in the same order of relative potency as on postjunctional α‐adrenoceptors in rabbit aortic strips.
In the concentrations used (30 μm), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [3H]‐noradrenaline from guinea‐pig atria.
The effect of clonidine, a partial agonist on prejunctional α‐adrenoceptors in guinea‐pig atria, in increasing stimulation‐induced efflux of [3H]‐noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 μm) and reversed by phentolamine (3 μm) and burimamide (30 μm).
THE EFFECTS OF SODIUM CROMOGLYCATE ON LUNG IRRITANT RECEPTORS AND LEFT VENTRICULAR CARDIAC RECEPTORS IN THE ANAESTHETIZED DOG
Authors: DIXON M. , JACKSON D.M. , RICHARDS I.M. 
Published: July 2012

The time from the injection of sodium cromoglycate 10 to 50 μg/kg into a saphenous vein, the cervical carotid arteries, the left ventricle and the aortic arch, to the onset of reflex hypotension has been measured in anaesthetized dogs. The shortest latency was 16.9 s on injection of sodium cromoglycate into the left ventricle.
Instillation of 2% lignocaine into the pericardium of an anaesthetized dog blocked the reflex hypotensive response to sodium cromoglycate (10 to 50 μg/kg i.v.), and also prevented sodium cromoglycate (100 μg/kg) from reversing reflex bronchoconstriction induced by inhalation of an aerosol of histamine.
The effect of sodium cromoglycate (100 μg/kg i.v.) on resting discharge and histamine‐induced discharge (20 μ/kg i.v.) of five lung irritant receptors in five anaesthetized dogs has been studied. Sodium cromoglycate (100 μg/kg i.v.) did not affect the resting discharge of these receptors or their ability to respond to histamine.
Sodium cromoglycate (100 μg/kg i.v.) increased the rate of discharge of three receptors found in the endocardium of the left ventricle of the canine heart. A solution of sodium cromoglycate (0.1%) was applied topically to one receptor and its rate of discharge was increased.
It is suggested that in the dog, sodium cromoglycate produces reflex hypotension and reverses histamine‐induced reflex bronchoconstriction by activating receptors in the left ventricle of the heart.
PURINE ANTAGONISTS IN THE IDENTIFICATION OF ADENOSINE‐RECEPTORS IN GUINEA‐PIG TRACHEA AND THE ROLE OF PURINES IN NON‐ADRENERGIC INHIBITORY NEUROTRANSMISSION
Authors: COLEMAN R.A. 
Published: July 2012

To test the possibility that adenosine receptors exist within the trachea of the guinea‐pig, an attempt has been made to identify a compound with adenosine antagonist activity in this tissue.
Quinidine, phentolamine, phenoxybenzamine, 2–2′‐pyridylisatogen tosylate (PIT) and caffeine were tested for antagonism of spasmolytic responses to adenosine, adenosine 5′‐triphosphate (ATP) and adenine on the guinea‐pig isolated trachea.
Quinidine (10 and 25 μg/ml), phentolamine (10 and 30 μg/ml) and phenoxybenzamine (10 μg/ml) had little or no effect on response to adenosine, ATP and adenine. PIT (21 μg/ml) potentiated responses to adenosine, ATP and adenine by an unexplained mechanism.
Caffeine (25 μg/ml) partially relaxed the trachea and inhibited spasmolytic responses to both adenosine and ATP, but not to adenine, isoprenaline, aminophylline or prostaglandin E2 (PGE2).
A number of compounds related to caffeine (xanthine, hypoxanthine, theophylline and theobromine) were tested for adenosine antagonist activity. Xanthine (300 μg/ml) and hypoxanthine (300 μg/ml) did not relax the trachea or antagonize spasmolytic responses to adenosine. Both theophylline (10 μg/ml) and theobromine (30 μg/ml) partially relaxed the trachea; theophylline, but not theobromine, antagonized spasmolytic responses to adenosine.
pA2 values for caffeine and theophylline as antagonists of adenosine were 4.3 and 4.7 respectively. However, the slopes of the Schild plot regressions were significantly less than 1.0 for both compounds.
Four compounds, adenine, AH 8883, M30966 and ICI 63197, which like caffeine and theophylline, have phosphodiesterase inhibitory activity were tested for adenosine antagonist activity in the trachea. Adenine and AH 8883 had no effect and M30966 and ICI 63197 caused significant potentiation.
The effects of caffeine and theophylline were also investigated on the non‐adrenergic inhibitory response to nerve stimulation (NAIR). Both caffeine (100 μg/ml, n = 4) and theophylline (30 μg/ml, n = 4) enhanced the NAIR (20 Hz) while virtually abolishing matched responses to exogenous adenosine.
The results support the existence of adenosine receptors in the guinea‐pig trachea.
HYDRALAZINE: EFFECT ON THE OUTFLOW OF NORADRENALINE AND MECHANICAL RESPONSES EVOKED BY SYMPATHETIC NERVE STIMULATION OF THE RAT TAIL ARTERY
Authors: CHEVILLARD C. , MATHIEU M.N. , SAIAG B. , WORCEL M. 
Published: July 2012

The effects of hydralazine on the vasoconstrictor responses to field stimulation of sympathetic nerves were studied in the isolated proximal segments of the rat tail artery. Vasoconstrictor responses to transmural stimulation were depressed by superfusion of hydralazine (0.3, 3 and 30μm) in a concentration‐dependent manner. The inhibition appeared slowly and was not easily reversed by washing.
Hydralazine (30 nm, 0.3 and 3 μm) reduced the stimulation‐induced overflow of tritium from proximal and distal segments of the tail artery labelled with [3H]‐noradrenaline in a concentration‐dependent manner. This phenomenon appeared rapidly and was easily reversed by washing.
Theophylline (0.5 mm) did not affect the inhibitory effect of hydralazine on the stimulation‐induced tritium efflux from the distal segment of the rat tail artery.
The present results indicate that hydralazine has, in addition to its action on vascular smooth muscle, a very marked effect on sympathetic nerve terminals. The mechanism of this presynaptic inhibition appears to be different from the postsynaptic effect, in view of the much shorter delay, the shape of the dose‐effect curve, and the lack of interaction with theophylline.