VASOCONSTRICTION OF GUINEA-PIG SUBMUCOSAL ARTERIOLES FOLLOWING SYMPATHETIC-NERVE STIMULATION IS MEDIATED BY THE RELEASE OF ATP

1 The nature of the transmitter mediating vasoconstriction of guinea-pig submucosal arterioles following sympathetic nerve stimulation was studied. 2 Prazosin (0.1-mu-M) abolished the response to exogenously applied phenylephrine (1-mu-M) but had no effect on constrictions of submucosal arterioles evoked by nerve stimulation (100 pulses at 10 Hz). 3 Vasoconstrictions and excitatory junction potentials elicited by nerve stimulation were potentiated by idazoxan (0.1-mu-M). 4 Following reserpine treatment, catecholamine fluorescence was absent in submucosal arterioles but nerve-evoked vasoconstrictions were unaltered. 5 Vasoconstrictions and excitatory junction potentials recorded in response to sympathetic nerve stimulation, as well as constrictions evoked by exogenously applied ATP (3-mu-M), were abolished by the P2-purinoceptor antagonist, suramin (100-mu-M). Suramin had no effect on the vasoconstriction in response to noradrenaline (3-mu-M), or the nicotinic excitatory postsynaptic potentials (e.p.s.ps) and noradrenergic inhibitory postsynaptic potentials (i.p.s.ps) recorded from submucosal neurones. 6 We conclude that postjunctional responses of submucosal arterioles following sympathetic nerve stimulation are mediated solely through the activation of P2x-purinoceptors by ATP or a related purine nucleotide. The function of neurally released noradrenaline is to act through prejunctional alpha-2-adrenoceptors to depress transmitter release.