Spinal cord substance P mediates the inhibition of gastric acid secretion induced by electrical stimulation of the preoptic area.

A possible role of spinal substance P (SP) in the mediation of signals to inhibit gastric acid secretion by central activation of the sympatho-adrenomedullary system was examined in urethane-anesthetized rats. Intrathecal (i.t.) administration of SP (1-10 nmol) inhibited vagally induced acid output. I.t. administration of spantide, a SP receptor antagonist, reduced the inhibitory effect of 3 nmol SP. I.t. administration of spantide (0.1-1 nmol) blocked the inhibition of vagally induced gastric acid output evoked by electrical stimulation of the preoptic area. Atropine, hexamethonium, phentolamine, propranolol, DL-para-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine (5,7-DHT) were without effect. Repeated i.t. administration of 10 nmol SP produced desensitization to the SP-induced inhibitory response on gastric acid output. In these animals, electrical stimulation of the preoptic area did not inhibit vagally induced gastric acid output. These results suggest that electrical stimulation of the preoptic area excites SP-containing neurons in the spinal cord, and a resultant sympatho-adrenomedullary system-mediated inhibition of gastric acid secretion occurs.