Inhibition of antidromically induced stimulation of gastric motility by substance P receptor blockade.

Electrical stimulation of the feline vagal or splanchnic nerves after hexamethonium blockade of nicotinic ganglionic transmission produces gastric contractions, suggesting antidromic activation of thin afferents. The present experiments were performed to examine whether substance P is involved as a transmitter in such gastric responses. Cats were anesthetized with chloralose, laparotomized and the adrenals were ligated. The left greater splanchnic nerve, proximal to the celiac ganglion, and the left or right cervical vagal nerve were dissected, cut and placed on electrodes for peripheral stimulation. Gastric motility was monitored with a balloon. Hexamethonium was administered i.v. as well as i.a. to the stomach. Nerve stimulations produced powerful gastric contractions, which were antagonized by large doses (approximately 0.8 mumol) of substance P administered i.a. to the stomach. Similarly, the gastric contractions elicited by vagal or splanchnic nerve stimulations were reduced to at least 60% of control by the specific substance P antagonist (D-Pro2, D-Trp7,9)-SP administered i.a. (0.4-1.3 mumol). The present results support the concept that substance P is associated with gastric excitatory motor responses, possibly elicited by antidromic activation of thin afferent nerve fibres.