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 fistula and a Heidenhain pouch, by using the putative mu-opioid receptor agonist dermorphin, the delta-opioid receptor agonist [D-Ala2,D-Leu5]enkephalin (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 dynorphin-(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 gastric 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 or 2-deoxy-D-glucose-stimulated conditions. Submaximal bethanechol-stimulated secretion was increased by dermorphin and DADLE but unaffected by dynorphin-(1-13). Acid secretion from the gastric fistula stimulated by pentagastrin was enhanced by dermorphin, inhibited by DADLE and unaffected by dynorphin-(1-13). Dermorphin and DADLE significantly increased acid secretion from the Heidenhain pouch stimulated by pentagastrin, while dynorphin-(1-13) was ineffective. Naloxone prevented the stimulatory 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 gastric fistula were prevented by naltrindole, a selective antagonist of delta-opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Intorre
L
L
Laboratory of Pharmacology, Institute of Veterinary Internal Medicine, Pisa, Italy.
Mengozzi
G
G
Vanni
E
E
Grassi
F
F
Soldani
G
G
D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology; D004285:Dogs; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005755:Gastrins / Q000097:blood*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides; D011957:Receptors, Opioid / Q000502:physiology*; D017465:Receptors, Opioid, delta / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000502:physiology
D005755:Gastrins; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C030058:dermorphin; D016308:Enkephalin, Leucine-2-Alanine; D003847:Deoxyglucose