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The effects of [Arg14, Lys15] nociceptin/orphanin FQ, a highly potent agonist of the NOP receptor, on in vitro and in vivo gastrointestinal functions.
Peptides 2005; 26(9):1590-7P

Abstract

Nociceptin/orphanin FQ (N/OFQ) administered into the lateral left cerebral ventricle of rats has been reported to inhibit in vivo gut motor and secretory functions. Recently, a novel N/OFQ analog, [Arg14, Lys15] N/OFQ, was synthesized and demonstrated to behave as a highly potent agonist at the human recombinant N/OFQ peptide (NOP) receptors and to produce long-lasting effects in vivo in mice compared with the natural ligand N/OFQ. In the present study, the pharmacological profile of [Arg14, Lys15] N/OFQ was further evaluated and compared with that of N/OFQ in vitro on guinea pig exocrine pancreas and in vivo on gastric emptying, colonic propulsion and gastric acid secretion in rats. [Arg14, Lys15] N/OFQ and N/OFQ significantly decreased the KCl-evoked amylase secretion from isolated pancreatic lobules of the guinea pig. In in vivo experiments, [Arg14, Lys15] N/OFQ mimicked the effects of N/OFQ, inducing, after intracerebroventricular injection, a delay (up to 70%) in the gastric emptying of a phenol red meal, an increase (about 40 times) of the mean bead colonic expulsion time and a decrease (up to 90%) of gastric acid secretion in water loaded rats after 90 min pylorus ligature. In all these assays, [Arg14, Lys15] N/OFQ was more effective than N/OFQ, and its effective doses were at least 10-fold lower than N/OFQ effective doses. The highly selective NOP receptor antagonist, UFP-101, decreased the efficacy of [Arg14, Lys15] N/OFQ in in vitro and in vivo assays above reported. These findings: (a) show that pancreatic NOP receptors mediate an in vitro inhibitory effect on stimulated guinea pig amylase secretion; (b) confirm that the stimulation of central NOP receptors exerts an inhibitory control on gastric emptying, colonic motility and gastric secretion in rats and (c) put in evidence that [Arg14, Lys15] N/OFQ, being more potent and effective than the natural ligand N/OFQ, represents a new pharmacological tool for the study of the physiological and pharmacological roles mediated by the N/OFQ-NOP receptor system.

Authors+Show Affiliations

Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Ple A. Moro 5-00185 Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16112397

Citation

Broccardo, M, et al. "The Effects of [Arg14, Lys15] Nociceptin/orphanin FQ, a Highly Potent Agonist of the NOP Receptor, On in Vitro and in Vivo Gastrointestinal Functions." Peptides, vol. 26, no. 9, 2005, pp. 1590-7.
Broccardo M, Linari G, Guerrini R, et al. The effects of [Arg14, Lys15] nociceptin/orphanin FQ, a highly potent agonist of the NOP receptor, on in vitro and in vivo gastrointestinal functions. Peptides. 2005;26(9):1590-7.
Broccardo, M., Linari, G., Guerrini, R., Agostini, S., Petrella, C., & Improta, G. (2005). The effects of [Arg14, Lys15] nociceptin/orphanin FQ, a highly potent agonist of the NOP receptor, on in vitro and in vivo gastrointestinal functions. Peptides, 26(9), pp. 1590-7.
Broccardo M, et al. The Effects of [Arg14, Lys15] Nociceptin/orphanin FQ, a Highly Potent Agonist of the NOP Receptor, On in Vitro and in Vivo Gastrointestinal Functions. Peptides. 2005;26(9):1590-7. PubMed PMID: 16112397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effects of [Arg14, Lys15] nociceptin/orphanin FQ, a highly potent agonist of the NOP receptor, on in vitro and in vivo gastrointestinal functions. AU - Broccardo,M, AU - Linari,G, AU - Guerrini,R, AU - Agostini,S, AU - Petrella,C, AU - Improta,G, Y1 - 2005/03/19/ PY - 2004/12/17/received PY - 2005/02/18/revised PY - 2005/02/21/accepted PY - 2005/8/23/pubmed PY - 2005/12/24/medline PY - 2005/8/23/entrez SP - 1590 EP - 7 JF - Peptides JO - Peptides VL - 26 IS - 9 N2 - Nociceptin/orphanin FQ (N/OFQ) administered into the lateral left cerebral ventricle of rats has been reported to inhibit in vivo gut motor and secretory functions. Recently, a novel N/OFQ analog, [Arg14, Lys15] N/OFQ, was synthesized and demonstrated to behave as a highly potent agonist at the human recombinant N/OFQ peptide (NOP) receptors and to produce long-lasting effects in vivo in mice compared with the natural ligand N/OFQ. In the present study, the pharmacological profile of [Arg14, Lys15] N/OFQ was further evaluated and compared with that of N/OFQ in vitro on guinea pig exocrine pancreas and in vivo on gastric emptying, colonic propulsion and gastric acid secretion in rats. [Arg14, Lys15] N/OFQ and N/OFQ significantly decreased the KCl-evoked amylase secretion from isolated pancreatic lobules of the guinea pig. In in vivo experiments, [Arg14, Lys15] N/OFQ mimicked the effects of N/OFQ, inducing, after intracerebroventricular injection, a delay (up to 70%) in the gastric emptying of a phenol red meal, an increase (about 40 times) of the mean bead colonic expulsion time and a decrease (up to 90%) of gastric acid secretion in water loaded rats after 90 min pylorus ligature. In all these assays, [Arg14, Lys15] N/OFQ was more effective than N/OFQ, and its effective doses were at least 10-fold lower than N/OFQ effective doses. The highly selective NOP receptor antagonist, UFP-101, decreased the efficacy of [Arg14, Lys15] N/OFQ in in vitro and in vivo assays above reported. These findings: (a) show that pancreatic NOP receptors mediate an in vitro inhibitory effect on stimulated guinea pig amylase secretion; (b) confirm that the stimulation of central NOP receptors exerts an inhibitory control on gastric emptying, colonic motility and gastric secretion in rats and (c) put in evidence that [Arg14, Lys15] N/OFQ, being more potent and effective than the natural ligand N/OFQ, represents a new pharmacological tool for the study of the physiological and pharmacological roles mediated by the N/OFQ-NOP receptor system. SN - 0196-9781 UR - https://www.unboundmedicine.com/medline/citation/16112397/The_effects_of_[Arg14_Lys15]_nociceptin/orphanin_FQ_a_highly_potent_agonist_of_the_NOP_receptor_on_in_vitro_and_in_vivo_gastrointestinal_functions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(05)00074-4 DB - PRIME DP - Unbound Medicine ER -