THE ROLE OF PERIPHERAL OPIOID RECEPTOR SUBTYPES IN THE MODULATION OF GASTRIC-ACID SECRETION AND PLASMA GASTRIN IN DOGS

The peripheral opioid receptor subtypes involved in the regulation of gastric acid secretion were studied in dogs with both a gastric fistul a and a Heidenhain pouch, by using the putative mu-opioid receptor ago nist dermorphin, the delta-opioid receptor agonist [D-Ala2,D-Leu5]enke phalin (DADLE) and the kappa-opioid receptor agonist dynorphin-(1-13). Dermorphin caused a significant increase in basal acid secretion from both the gastric fistula and the Heidenhain pouch, while DADLE and dy norphin-(1-13) did not. Acid secretion stimulated by 2-deoxy-D-glucose from the gastric fistula was not modified by dermorphin and dynorphin -(1-13), while DADLE significantly inhibited it; at the same time gast ric secretion from the Heidenhain pouch was significantly increased by dermorphin and unmodified by DADLE and dynorphin-(1-13). Dermorphin, DADLE or dynorphin-(1-13) did not modify plasma gastrin during basal o r 2-deoXy-D-glucose-stimulated conditions. Submaximal bethanechol-stim ulated secretion was increased by dermorphin and DADLE but unaffected by dynorphin-(1-13). Acid secretion from the gastric fistula stimulate d by pentagastrin was enhanced by dermorphin, inhibited by DADLE and u naffected by dynorphin-(1-13). Dermorphin and DADLE significantly incr eased acid secretion from the Heidenhain pouch stimulated by pentagast rin, while dynorphin-(1-13) was ineffective. Naloxone prevented the st imulatory effects of dermorphin and DADLE on the Heidenhain pouch, but it reduced acid secretion from the gastric fistula further when given with DADLE. The inhibitory effects of DADLE on secretion from the gas tric fistula were prevented by naltrindole, a selective antagonist of delta-opioid receptors. We conclude that peripheral mu-opioid receptor s mediate excitatory effects, delta-opioid receptors produce mainly in hibitory effects, while kappa-opioid receptors do not seem to be invol ved in the regulation of acid secretion. Further, measurements of plas ma gastrin suggest that the opioid-induced changes in acid secretion a re not due to variations in gastrin release.