Effect of labetalol on adrenergic transmission in the rat anococcygeus muscle [proceedings].
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Biomedical subjects
Publications and source records attributed to S A Doggrell.
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The contractile responses of the rat anococcygeus muscle to sympathomimetics, dopaminergic agonists and 5-hydroxytryptamine, but not to acetylcholine, were inhibited by phentolamine (10(-5)M). Following 6-hydroxydopamine incubation (10(-3)M for 3h), the accumulation of noradrenaline was inhibited, contractile responses to noradrenaline were potentiated, responses to tyramine were abolished and responses to acetylcholine were unaltered. Thus, any spasmogen activity due to release of noradrenaline in this muscle was abolished by 6-hydroxydopamine incubation. This method was used to characterise the direct and indirect actions of some sympathomimetics. In addition, dopaminergic agonists and 5-hydroxytryptamine may also act by releasing noradrenaline in this preparation.
The effects of phentolamine (10(-6)M) and prazosin (10(-7)M) on contractile responses, in the presence of cocaine or nortriptyline, were investigated in vas deferens and anococcygeus muscle of rat. Cocaine (10(-5)M) and nortriptyline (10(-6)M) had no effect on maximum responses to field stimulation, (--)-noradrenaline, methoxamine, and acetylcholine in anococcygeus muscle. However, both cocaine (3.3 x 10(-5)M) and nortripthline (10(-6)M) potentiated maximum responses to (--)-noradrenaline without altering the maximum response to field stimulation in vas deferens. In vas deferens, phentolamine potentiated or inhibited the responses to field stimulation depending on the frequency whereas prazosin inhibited all responses to field stimulation. In anococcygeus muscle, both phentolamine and prazosin inhibited all responses to field stimulation. In vas deferens and anococcygeus muscle, prazosin was a more potent antagonist of responses to (--)-noradrenaline than phentolamine. These results show that prazosin is a more potent postsynaptic alpha-adrenoceptor antagonist than phentolamine and suggest that prazosin has little or no affinity for presynaptic alpha-adrenoceptors.
1 The effect of a series of antidepressant drugs on noradrenaline accumulation was studied in the isolated anococcygeus muscle of the rat. 2 The most potent inhibitors of noradrenaline accumulation were nortriptyline, desipramine and protriptyline. Opipramol, trimipramine and iprindole were active only in high concentrations. 3 Contractions of the anococcygeus muscle produced by noradrenaline were strongly potentiated by nortriptyline, desipramine and protriptyline. Other uptake inhibitors were less active in potentiating the noradrenaline response. 4 Nortriptyline, in concentrations that potentiated the action of noradrenaline, reduced or abolished the response to tyramine.
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