Effect of selective mu 1, mu 2 and delta 2 opioid receptor agonists on gastric functions in the rat

Because the role of mu and delta opioid receptors in modulating gastric functions remains uncertain, we studied whether intracerebroventricular (i.c.v.) and subcutaneous (s.c.) injections of new opioid peptides with high selectivity for mu 1 (Lys7-dermorphin), mu 2 (Trp4-Asn7-dermorphin) and delta 2 (D-Ala2-deltorphin II) opioid receptors would modify gastric secretion (after 2 hr pylorus ligature) and transit (after a phenol red meal) in the rat. Neither i.c.v. nor s.c. injections of the delta 2 opioid agonist affected the gastric functions. In contrast, the mu opioid agonists decreased gastric acid secretion and emptying, i.c.v. injections inducing more potent inhibition than s.c. administration. The mu 1 selective opioid antagonist naloxonazine had no effect on the inhibition of the gastric secretory and motor response to these peptides but naloxone completely blocked their effects. Our findings suggest (1) that in rats, stimulation of central naloxonazine insensitive opioid receptors (mu 2 sites) inhibits gastric acid secretion and emptying; and (2) that delta opioid receptors take no part in mediating these functions.