1 a2-Autoinhibition of transmitter release was investigated in the largest rami caecales of the rabbit ileocolic artery. Vasoconstriction, elicited by electrical field stimulation or by exogenous agonists, was measured as an increase in perfusion pressure. 2 Short periods of electrical stimulation elicited monophasic vasoconstriction, whereas longer periods (> 10s) produced biphasic vasoconstriction. Prazosin had no significant effect on the first component of the biphasic vasoconstriction elicited by electrical stimulation, but did reduce the second component at higher frequencies. a,fi-Methylene ATP significantly attenuated the first component whilst the second component was relatively resistant. 3 The x2-adrenoceptor antagonist yohimbine did not change responses evoked by very short pulse trains (<2 s) but enhanced responses to longer pulse trains. When vasoconstriction was biphasic, both phases were potentiated by yohimbine. 4 The results indicate that the vasoconstriction elicited by brief trains of sympathetic nerve impulses is mainly or exclusively mediated by ATP, whereas at longer pulse trains a noradrenergic component comes into play. The potentiation produced by yohimbine is due to interruption of presynaptic a2-adrenoceptor-mediated autoinhibition of transmitter release. The autoinhibition affects both purinergic and adrenergic components of sympathetic neurotransmission.

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1 The pressor responses produced by the intravenous administration of a,#-methylene ATP were tachyphylactic.2 a,fi-Methylene ATP can attenuate pressor responses to sympathetic nerve stimulation both in the presence and in the absence of a-adrenoceptor blocking agents.3 a,#-Methylene ATP has no effect on the pressor responses produced by bolus injections of noradrenaline.4 In the presence of a-adrenoceptor blocking agents, a,x-methylene ATP further attenuates contractions of the vas deferens produced by nerve stimulation. 5 The results, together with previous data, suggest that the vasopressor response to stimulation of the sympathetic outflow in the rat is partly purinergic and partly a-adrenergic and that this occurs as co-transmission. The same applies to rat vas deferens, confirming in vitro data. The pithed rabbit had an a-blocker-resistant vasopressor nerve-mediated response but this was resistant to a,#-methylene ATP.