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Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: a comparative study.
Pharmacol Res. 2006 Nov; 54(5):356-60.PR

Abstract

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.

Authors+Show Affiliations

University La Sapienza, Fisiologia Umana e Farmacologia, Piazzale A. Moro 5, 00185 Roma, RM, Italy. giorgio.linari@uniromal.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16979347

Citation

Linari, Giorgio, et al. "Regulation of Pancreatic Secretion in Vitro By Nociceptin/orphanin FQ and Opioid Receptors: a Comparative Study." Pharmacological Research, vol. 54, no. 5, 2006, pp. 356-60.
Linari G, Agostini S, Broccardo M, et al. Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: a comparative study. Pharmacol Res. 2006;54(5):356-60.
Linari, G., Agostini, S., Broccardo, M., Petrella, C., & Improta, G. (2006). Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: a comparative study. Pharmacological Research, 54(5), 356-60.
Linari G, et al. Regulation of Pancreatic Secretion in Vitro By Nociceptin/orphanin FQ and Opioid Receptors: a Comparative Study. Pharmacol Res. 2006;54(5):356-60. PubMed PMID: 16979347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of pancreatic secretion in vitro by nociceptin/orphanin FQ and opioid receptors: a comparative study. AU - Linari,Giorgio, AU - Agostini,Simona, AU - Broccardo,Maria, AU - Petrella,Carla, AU - Improta,Giovanna, Y1 - 2006/08/15/ PY - 2006/05/12/received PY - 2006/07/05/revised PY - 2006/07/10/accepted PY - 2006/9/19/pubmed PY - 2007/1/11/medline PY - 2006/9/19/entrez SP - 356 EP - 60 JF - Pharmacological research JO - Pharmacol. Res. VL - 54 IS - 5 N2 - 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. SN - 1043-6618 UR - https://www.unboundmedicine.com/medline/citation/16979347/Regulation_of_pancreatic_secretion_in_vitro_by_nociceptin/orphanin_FQ_and_opioid_receptors:_a_comparative_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-6618(06)00145-9 DB - PRIME DP - Unbound Medicine ER -