Role_1984_Proc.Natl.Acad.Sci.U.S.A_81_2924

Substance P has been identified by combined immunohistochemical and radioimmunological techniques to be present in preganglionic cholinergic and sensory nerve fibers of amphibian, mammalian, and avian autonomic ganglia. The peptide has been shown to depolarize sympathetic neurons of frog and guinea pig and to decrease the cholinergic activation of Na+ influx and catecholamine release from chromaffin cells. The aim of this study was to examine the interaction of acetylcholine and substance P on autonomic neurons. This report demonstrates a direct effect of substance P on acetylcholine-induced inward currents in both sympathetic and parasympathetic neurons clamped near resting membrane potential. Under these conditions, substance P dramatically enhances the rate of decay of the inward current in the continued presence of agonist without substantially affecting peak inward current. This effect is consistent with an enhancement of acetylcholine-receptor desensitization. Since substance P-containing cell bodies have been demonstrated in the avian (preganglionic) column of Terni as well as in fibers from the nucleus of Edinger-Westphal, the observed peptide inhibition of cholinergic activation of the neurons may function physiologically to modulate synaptic function in autonomic ganglia.