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Biomedical subjects

M A Zar

Publications and source records attributed to M A Zar.

At least 37 records · Page 2Linked to original sources
PubMed1987

Inhibition of non-adrenergic transmission in the rat vas deferens by prazosin.

Isolated preparations of rat vas deferens were induced to contract by neurogenic and non-neurogenic stimuli, and the effect of prazosin on these contractions was investigated. Prazosin (24 microM) exerted a profound inhibitory effect on neurogenic contractions and had no significant effect on non-neurogenic contractions. These experiments indicate that prazosin is capable of interacting with the neurotransmission processes in the vas deferens to produce inhibition of transmission.

Animals↗
PubMed1982

Effect of metoclopramide in guinea-pig ileum longitudinal muscle: evidence against dopamine-mediation.

The investigation examines the hypothesis that metoclopramide-induced potentiation of gastrointestinal motility is mediated through dopamine receptors. In vitro studies on the longitudinal muscle of the guinea-pig ileum were performed. Metoclopramide, in concentrations comparable with those seen in plasma after therapeutic doses in man, selectively potentiated the cholinergic response Dopamine (1-100 microM) inhibited cholinergic transmission by inhibiting neuronal acetylcholine release. The inhibitory action of dopamine was antagonised by phentolamine, and alpha-adrenoceptor antagonist, but not by the dopamine receptor antagonists metoclopramide or primozide. Bromocriptine inhibited cholinergic responses by a postsynaptic mechanism which was not antagonised by metoclopramide, primozide, or phentolamine. The results are consistent with the view that metoclopramide-induced potentiation of gastrointestinal motility does not involve local dopamine receptors.

Animals↗
PubMed1981

Actions of the crude venom of the Sydney funnel-web spider. Atrax robustus on autonomic neuromuscular transmission.

1 The effects on mammalian autonomic neuromuscular transmission of the crude venom of the female Sydney funnel-web spider Atrax robustus, have been investigated.2 At doses of 10 mug/ml or lower the indirectly elicited twitch-like responses of the rat anococcygeus preparation were inhibited. At doses greater than 10 mug/ml there was an initial reduction in the twitch-like response followed by a sustained contracture of the tissue.3 The long-lasting contracture caused by the venom was abolished by the application of phentolamine. It was virtually non-existent in muscle preparations isolated from reserpine-treated rats.4 In the presence of tetrodotoxin the contracture was smaller and less well maintained than in its absence.5 The venom caused a small reduction in the amplitude of the indirectly elicited twitch-like response of the longitudinal muscle of the guinea-pig ileum, followed by an increase in the tone of the preparation. The increase in tone was maintained for several minutes and was rapidly abolished by the application of atropine. The presence of venom did not affect control responses to either histamine or acetylcholine.6 Inhibitory transmission in the rat anococcygeus preparation was unaffected by the venom.7 The neurally-mediated twitch-like responses of both guinea-pig and rat vas deferens were inhibited by the venom at doses below 10 mug/ml. At higher doses the inhibition was accompanied by spontaneous contractions, and at doses in excess of 100 mug/ml the inhibition of twitch-like responses was transient and was followed by a potentiation of the motor response and extensive spontaneous activity. The preparation became quiescent 20 min after the application of venom and the evoked response was abolished after 60 min.8 The venom had qualitatively similar effects on motor transmission in the human vas deferens as on the rat and guinea-pig preparations. However, the human preparations were 50 to 100 times more sensitive to the effects of the venom.

Animals↗
PubMed1978

The effects of a toxin isolated from Australian tiger snake (Notechis scutatus scutatus) venom on autonomic neuromuscular transmission.

1 The effects on mammalian autonomic neuromuscular transmission of a purified toxin from the crude venom of the Australian tiger snake, Notechis scutatus, have been investigated. 2 The toxin had no measurable effect on transmission in either the rat anococcygeus, the rat vas deferens, or the longitudinal muscle of the guinea-pig ileum. 3 The toxin induced a contraction of longitudinal smooth muscle of the ileum. The tissue relaxed in spite of the continued presence of the toxin, and remained insensitive to further doses. The contractile response was not mediated by either cholinergic or histaminergic mechanisms. 4 The toxin caused an inhibition of the response to field stimulation of the guinea-pig vas deferens and the guinea-pig seminal vesicle. The inhibition was spontaneously reversible, and the preparations remained insensitive to further doses fo the toxin. The effects of the toxin were not mediated by either prostaglandins or by noradrenaline. 5 The inhibitory effects of a variety of compounds known to act at presynaptic sites were also blocked by exposure to the toxin; inhibition caused by postsynaptic activity was unaffected by the toxin. 6 It is suggested that the toxin inhibits transmission in the guinea-pig vas deferens and seminal vesicle by a presynaptic mechanism. 7 The possibility that the mechanism involves phospholipase A2 activity is discussed.

Animals↗
PubMed1977

Comprehensive clinical drug information service: first year's experience.

A comprehensive clinical drug information service, established in the Northern Region in May 1975, is manned by eight doctors--all clinical pharmacologists--and is available 24 hours a day. In the first year of operation 451 inquiries were received, 354 (78-5%) of which were "consultative." Though junior hospital doctors used the service most, almost half of the inquiries about adverse reactions to drugs came from consultants.

Drug Information Services↗
PubMed1975

Effects of lysergic acid diethylamide on autonomic post-ganglionic transmission.

1. Six sites of autonomic post-ganglionic transmission were examined for susceptibility to LSD. Inhibition of transmission by LSD was confined to the three sympathetic junctions. 2. Inhibition of sympathetic transmission was maximal with short trains of pulses and declined considerably as train length was increased. 3. Evidence for a presynaptic mode of action was obtained. This was the predominant effect of LSD in the rat anococcygeus and dog retractor penis because alpha-adrenoceptor-blocking properties were feeble or absent; but in dog splenic strips LSD produced marked post-synaptic alpha-blockade. 4. The presynaptic inhibitory effect of LSD was unrelated to its 5-hydroxytryptamine-blocking property because it was not shared by methysergide. Neither was it mediated by prostaglandin release because it was unaltered by indomethacin, which suppresses prostaglandin synthesis. 5. In the rat anococcygeus and dog retractor penis larger doses of LSD induced slow contractions and, as a result of the concurrent block of motor transmission, revealed relaxation responses on transmural stimulation, caused by the excitation of sacral inhibitory fibres present in these muscles. 6. The LSD contractions were due to stimulation of post-synaptic alpha-adrenoceptors because they were abolished by phentolamine or yohimbine but were present as usual in preparations taken from reserpinized animals. 7. LSD blocked presynaptic alpha-adrenoceptors in the cholinergic motor fibres to the longitudinal muscle of the guinea-pig ileum.

Adrenergic alpha-Antagonists↗
PubMed1974

The rabbit rectococcygeus: a ganglion-free parasympathetically innervated preparation.

1 Isolated, desheathed preparations of the rabbit rectococcygeus muscle were relatively insensitive to spasmogens other than muscarinic drugs. Transmural stimulation with 1-50 pulses (0.2-0.4 ms at 10 Hz) elicited graded twitches which were abolished by tetrodotoxin and were therefore neurogenic; longer pulses sometimes triggered tetrodotoxin-resistant myogenic contractions.2 Twitches elicited by 0.2-0.4 ms pulses were due to post-ganglionic excitation because they were not reduced by hexamethonium, pentolinium or dimethyltubocurarine, or by ganglion-paralyzing concentrations of nicotine.3 The acetyl- and butyryl-cholinesterase activities of the rectococcygeus were determined manometrically and could be selectively inhibited by BW 284C51 (1:5-bis-(4-allyl-dimethylammonium-phenyl)-pentan-3-one dibromide) and iso-OMPA (tetramonoisopropylpyrophosphortetramide), respectively. Single-pulse twitches were greatly potentiated in amplitude and duration only when both cholinesterases were inhibited.4 The preparations could not be made to contract by nicotine (2.1-21 muM) even after cholinesterase inhibition, suggesting an absence of ganglion-cells; with nicotine (105-210 muM) small, atropine-susceptible responses were elicited, which were non-ganglionic because they were not reduced by tetrodotoxin.5 Rectococcygeus preparations that had been treated with physostigmine released acetylcholine into the bath fluid on electrical stimulation.6 The motor transmission was paralyzed by botulinum toxin (Type A) and abolished by atropine; the block of muscarinic receptors by atropine was effective against both endogenous and exogenous acetylcholine.7 Inhibitory adrenoceptors and scanty motor alpha-adrenoceptors were detected in the smooth muscle.8 Strong inhibitions of motor transmission and of rhythmic activity were produced by noradrenaline (but not by tyramine), by isoprenaline, and, after phentolamine, also by adrenaline and phenylephrine. These inhibitions were only slightly reduced by propranolol and rather more by pindolol.9 Experiments on preparations retaining their extrinsic nerve supply suggest an absence of ganglionic relays in the last 1-2 cm of the motor nerve pathway to this muscle.10 Some contrasting properties of the adjacent caudo-anal muscle, including the poor motor responses to transmural stimulation, are described.

Acetylcholine↗
PubMed1973

An inhibition of post-ganglionic motor transmission in the mammalian vas deferens by D-lysergic acid diethylamide.

1. Under certain conditions D-lysergic acid diethylamide (LSD), 10(-9)-10(-6) g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length. These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10(-9)-10(-6) g/ml., reaching a maximum at 0.5-1 x 10(-6) g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten- to twenty-fold increase in LSD concentration to 10(-5) g/ml. and were in fact slightly potentiated.4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an alpha-adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.5. The use of propranolol excluded mediation of the LSD-inhibition by beta-adrenoceptors.6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it was antagonized by phentolamine; another alpha-adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.

Acetylcholine↗