Evidence that substance P is a neurotransmitter in the myenteric plexus

Substance P (SP) is an undecapeptide originally isolated from the gut and since shown to occur within neurones in several parts of the peripheral and central nervous systems. Immunohistochemical studies indicate an exceedingly dense network of SP-containing nerves within the myenteric plexus of the guinea pig ileum. These nerves are intrinsic to the gut wall and can release SP to contract the longitudinal muscle layer. We have previously shown that SP directly depolarizes myenteric neurones and that this depolarization has a time course and ionic mechanism similar to the slow excitatory postsynaptic potential (e.p.s.p.) which can be produced by electrical stimulation of presynaptic nerves within the myenteric ganglia. We wondered whether SP might mediate this slow synaptic potential. We report here that the SP depolarization and the slow e.p.s.p. are reversibly depressed by chymotrypsin, an enzyme which degrades SP, although the responses to acetylcholine, serotonin and an unknown hyperpolarizing transmitter are unaffected. The results provide direct evidence that a peptide can mediate chemical transmission between neurones in the mammalian nervous system.