British journal of pharmacology
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1. Presynaptic receptor-mediated modulation of stimulation-evoked [3H]-acetylcholine[( 3H]-ACh) release from the neuromuscular junction was studied in the region of the mouse hemidiaphragm which contains the motor endplates, and which can easily be loaded with [3H]-choline. This method made it possible to detect exclusively the [Ca2+]0-dependent, quantal release of [3H]-ACh in response to axonal stimulation. 2. ⋯ It is concluded that quantally-released ACh from motor endplates is subject to prejunctional automodulation: (a) ACh facilitates its own release via an effect on prejunctional nicotinic receptors (positive feedback), (b) ACh release is reduced by an action on muscarinic receptors. When the nicotinic receptor-mediated facilitation is fully operative, the muscarinic receptor-mediated negative feedback is much less effective. It is supposed that there is a link between the two feedback mechanisms possibly at the level of the second messenger system(s).
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1. The effects of the anaesthetic alphaxalone (0.05 to 1 mM) on the node of Ranvier of isolated myelinated nerve fibres of the frog were studied under voltage-clamp conditions. 2. When added to the solution bathing voltage-clamped nodes, alphaxalone modified neither linear leakage nor capacitative currents but rapidly and reversibly blocked K and Na currents. ⋯ In contrast, the apparent dissociation constant for the Na current was almost constant with increasing voltages and equalled about 0.30 mM. Hill coefficient values for both K and Na currents were noticeably less than one. 6. It is concluded that, at higher concentrations than those attainable in the brain or in the plasma during surgical anaesthesia in man, alphaxalone has a 'local anaesthetic-like' action on the peripheral nervous system in that it specifically and differentially interacts with K and Na channel gating systems: it is suggested that the anaesthetic would preferentially modify open K and inactivated Na channels.
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1. Cardiac output, its distribution and regional vascular resistances were determined with tracer microspheres in pithed rats in the presence of the angiotensin converting enzyme inhibitor enalapril. The effects of enalapril on the cardiovascular responses elicited by either the alpha 1-adrenoceptor agonist phenylephrine or the alpha 2-adrenoceptor agonist xylazine were determined. 2. ⋯ Enalapril inhibited phenylephrine-induced vasoconstriction in the testes, fat, muscle, spleen and gastrointestinal tract. Enalapril also inhibited phenylephrine-induced changes in cardiac output distribution to the lungs and liver. The infusion of angiotensin II did not fully reverse the inhibitory effect of enalapril either on the phenylephrine-induced increases in diastolic blood pressure or on the vasoconstriction in the fat, spleen and gastrointestinal tract, but did reverse all other effects of enalapril.
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1. The effect of varying artificial respiratory volume (at a fixed rate of 54 min-1) on cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in control pithed rats or during pressor responses to either the alpha 1-adrenoceptor agonist phenylephrine or the alpha 2-agonist xylazine. Phenylephrine was investigated in the presence of propranolol (3 mg kg-1). ⋯ It also influenced the effects of phenylephrine on cardiac output distribution to the liver, epididimides and hepatosplanchnic bed and on blood flow through skeletal muscle and the large intestine. 6. Changes in respiratory volume of air ventilated pithed rats thus influence cardiac output, its distribution and regional blood flows. Such changes can also differently influence the responses of various vascular beds to phenylephrine whilst having no effect on their responses to xylazine.
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1. The effects of oral and subcutaneous administration of the non-steroidal anti-inflammatory drugs sodium salicylate, aspirin and indomethacin on ex vivo gastric mucosal release of leukotriene C4 (LTC4) prostaglandin E2 (PGE2), 6-oxo-PGF1 alpha and thromboxane B2 (TXB2) were investigated in rats under basal conditions as well as after challenge with ethanol. 2. Basal release of PGE2, 6-oxo-PGF1 alpha and TXB2 was inhibited by oral administration of aspirin (0.6-400 mgkg-1) and indomethacin (4 or 20 mgkg-1), but not by sodium salicylate (up to 400 mgkg-1), in a dose-dependent manner. ⋯ On the other hand, sodium salicylate, but not indomethacin or low doses of aspirin (up to 25mg kg 1), by an unknown mechanism inhibits stimulation of LTC4 biosynthesis by ethanol and simultaneously protects the gastric mucosa against ethanol-induced damage. Similar effects of high oral doses (> 100mgkg- 1) of aspirin might be due to significant formation of salicylate. These results suggest that there is a causal relationship between enhanced LTC4 biosynthesis and the development of ethanol-induced gastric injury.