Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: a comparative study.
The effects of nociceptin/orphanin FQ (N/OFQ) on gastrointestinal functions resemble those of classic analgesic opioid agonists. In this study, we compared changes in amylase release from guinea pig isolated pancreatic acini and lobules induced by the N/OFQ analogue [Arg(14),Lys(15)]N/OFQ and by the delta-receptor opioid agonist deltorphin. Carbachol strongly stimulated amylase release from isolated acini. Both peptides left baseline and carbachol-stimulated amylase secretion from pancreatic acini unchanged. Co-incubation of KCl-stimulated lobules with [Arg(14),Lys(15)]N/OFQ or deltorphin inhibited KCl-induced amylase release in a concentration-dependent manner. Although maximal inhibition of amylase release by [Arg(14),Lys(15)]N/OFQ and deltorphin had similar amplitude, [Arg(14),Lys(15)]N/OFQ was 100-fold more potent than deltorphin on a molar basis. The selective NOP-receptor antagonist [Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2) (UFP-101) antagonized [Arg(14),Lys(15)]N/OFQ-induced inhibition but left deltorphin-induced inhibition unchanged. The selective delta opiate receptor antagonist naltrindole had no effect on [Arg(14),Lys(15)]N/OFQ inhibition but partly prevented the inhibition by deltorphin. [Arg(14),Lys(15)]N/OFQ and deltorphin combined had no influence on each other. These findings show that [Arg(14),Lys(15)]N/OFQ inhibits pancreatic enzyme secretion by suppressing cholinergic transmission in intralobular nerve fibers, as previously reported for opioid agents. They suggest that [Arg(14),Lys(15)]N/OFQ inhibition of amylase release is mediated through the NOP receptor and not through the delta opioid receptor. The N/OFQ-NOP receptor system, like the delta opioid system, plays an inhibitory role in regulating exocrine pancreatic secretion.
Linari
Giorgio
G
University La Sapienza, Fisiologia Umana e Farmacologia, Piazzale A. Moro 5, 00185 Roma, RM, Italy. giorgio.linari@uniromal.it
Agostini
Simona
S
Broccardo
Maria
M
Petrella
Carla
C
Improta
Giovanna
G
D000681:Amylases / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011957:Receptors, Opioid / Q000819:agonists / Q000378:metabolism*; D000094942:Nociceptin Receptor
C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; C444644:nociceptin, Arg(14)-Lys(15)-; C059567:deltorphin; D009271:Naltrexone; D000681:Amylases; C055382:naltrindole; D000094942:Nociceptin Receptor