TACHYKININ-INDUCED INCREASE IN GASTRIC-MUCOSAL RESISTANCE - ROLE OF PRIMARY AFFERENT NEURONS, CGRP, AND NO

The tachykinins [Ala(5), beta-Ala(8)] neurokinin A-(4-10) {[Ala(5), be ta-Ala(8)]NKA-(4-10)} and NKA-(4-10) dose dependently protected agains t ethanol-induced gastric mucosal damage in rats (half-maximal inhibit ory dose, 46 and 48 nmol/kg, respectively). These effects were abolish ed by primary afferent nerve denervation, calcitonin gene-related pept ide (CGRP) immunoneutralization, the CGRP receptor antagonist human (h ) hCGRP-(8-37), and inhibition of nitric oxide (NO) biosynthesis by NG -nitro-L-arginine methyl ester. Tachykinin-induced protection occurred despite marked depression of gastric mucosal blood flow and was not a ssociated with increased acid secretion. NK2-receptor blockade antagon ized the protective effects of [Ala(5), beta-Ala(8)]NKA-(4-10) and NKA -(4-10), whereas NK1-receptor blockade was ineffective. Blockade of NK 2 but not NK1 receptors prevented by 65% the protection evoked by topi cal capsaicin without affecting capsaicin-induced hyperemia. We conclu de that the increase in gastric mucosal resistance evoked by tachykini ns is NK2 receptor-mediated and involves primary afferent neurons, CGR P, and NO. Gastric mucosal hyperemia and increased acid secretion do n ot participate in the effect. Tachykinins activating NK2 receptors con tribute to the increase in gastric mucosal resistance but not the incr ement in mucosal blood flow after primary afferent nerve stimulation b y capsaicin.