Abstract
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 depolarizes sympathetic neurons of frog and guinea pig and to decrease the cholinergic activation of Na+ influx and catecholamine release from chromaffin cells. The interaction of acetylcholine and substance P on autonomic neurons was examined. A direct effect of substance P on acetylcholine-induced inward currents in both sympathetic and parasympathetic neurons clamped near resting membrane potential was demonstrated. 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 were 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.