CHARACTERIZATION OF THE OPIOID RECEPTOR TYPE MEDIATING INHIBITION OF RAT GASTRIC SOMATOSTATIN SECRETION

The opioid peptides are potent inhibitors of gastric somatostatin-like immunoreactivity (SLI) secretion from the isolated perfused rat stomach. In addition, inhibition of SLI secretion induced by vagal stimulation is partially blocked by naloxone, indicating that endogenously released opioid peptides probably play a physiological role in the regulation of SLI release. The opioid peptides exert their effects by interacting with a number of different receptor types. In the present study, the effects of the selective delta-opioid receptor agonists [D-Pen2,5]enkephalin and [D-Pen2,L-Pen5]enkephalin and the mu-receptor agonist ]D-Ala2, N-methyl (NMe)-Phe4, Gly5-ol[ekephalin on gastric inhibitory polypeptide (GIP)-stimulated SLI secretion from the isolated perfused rat stomach have been studied. Responses to the less selective delta-agonist [D-Ala2, D-Leu5]enkephalin, dynorphins 1-8,1-13, and 1-17, and the extended enkephalin forms Metenkephalin-Arg6-Phe7, Met-enkephalin-Arg6-Gly7-Leu8, and Met-enkephalin-Arg6-Arg7-Val8-NH2 (metorphamide), have also been investigated. [D-Ala2,NMe-Phe4,Gly5-ol]enkephalin induced a concentration-dependent inhibition of GIP-stimulated SLI secretion, with 50% of maximal inhibition at 10 nM. Neither [D-Pen2,5]enkephalin nor [D-Pen2,L-Pen5]enkephalin (10 nM to 1-mu-M) had any effect on SLI release, and [D-Ala2,D-Leu5]enkephalin inhibited SLI release only at high concentrations. Met-enkephalin-Arg6-Phe7 and metorphamide both inhibited SLI release, whereas Met-enkephalin-Arg6-Gly7-Leu8 and the dynorphins had little or no effect. In conclusion, the strong inhibition of SLI secretion produced by [D-Ala2,NMe-Phe4,GLy5-ol]enkephalin and lack of major effect of [D-Pen2,5]-enkephalin, [D-Pen2,L-Pen5]enkephalin, and the dynorphins indicate that opioid peptide-induced inhibition was mediated by interaction with mu-receptors and that neither delta- or kappa-receptors play a significant role.