Substance P has biphasic effects on catecholamine secretion evoked by electrical stimulation of perfused rat adrenal...

The adrenal medulla is innervated by the splanchnic nerve which contains substance P-immunoreactive fibres originating in the dorsal root ganglia but whose function in the adrenal medulla is not known. In the present study, we have examined the effect of exogenous substance P on catecholamine secretion and [3H]-choline overflow evoked by field stimulation of the perfused rat adrenal gland. Substance P had biphasic effects on catecholamine secretion evoked by field stimulation: at the lower concentrations (10(-7)-3 x 10(-6) M), substance P facilitated catecholamine secretion whereas at higher concentrations (3 x 10(-5) M), substance P inhibited catecholamine secretion. The effects of substance P were long-lasting: substance P at all concentrations present during the second of three 6-min stimulations increased catecholamine secretion during the third stimulation. The enhancement of catecholamine secretion by substance P during field stimulation was not blocked by atropine but was substantially blocked by hexamethonium plus atropine. Substance P at all concentrations inhibited the evoked [3H]-choline overflow with a maximal inhibition of 60% (at 10(-6) M). In the absence of stimulation, substance P (10(-7)-3 x 10(-5) M) had no effect on the basal catecholamine secretion or basal [3H]-choline overflow. These results indicate that substance P has modulatory effects on adrenal catecholamine secretion and [3H]-choline overflow evoked by electrical stimulation. Presynaptically, substance P inhibits transmitter overflow from cholinergic nerve terminals and post-synaptically substance P has biphasic effects on catecholamine secretion dependent on the substance P concentration. These results suggest a functional role for substance P-containing fibres innervating the adrenal medulla.