Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors
Autore:
Hawkinson, JE; Acosta-Burruel, M; Espitia, SA;
Indirizzi:
CoCensys, Dept Biochem Pharmacol, Irvine, CA 92618 USA CoCensys Irvine CAUSA 92618 Dept Biochem Pharmacol, Irvine, CA 92618 USA
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 2-3, volume: 389, anno: 2000,
pagine: 107 - 114
SICI:
0014-2999(20000218)389:2-3<107:OAPISB>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORPHANIN-FQ; ORL1 RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; FUNCTIONAL EXPRESSION; BINDING-SITE; IN-VITRO; CLONING; AGONIST; RAT; MODULATION;
Keywords:
nociceptin; orphanin FQ; ORL1; opioid; opioid receptor; GTP gamma S;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Hawkinson, JE Elan Pharmaceut, 3760 Haven Ave, Menlo Park, CA 94025 USA Elan Pharmaceut 3760 Haven Ave Menlo Park CA USA 94025 5 USA
Citazione:
J.E. Hawkinson et al., "Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors", EUR J PHARM, 389(2-3), 2000, pp. 107-114

Abstract

Nociceptin (orphanin FQ) is the recently discovered peptide agonist for the orphan receptor opioid receptor-like 1 (ORL1). Despite the high sequence homology between ORL1 and the opioid receptors, most opioids lack affinity for the nociceptin receptor. The affinity and functional profile of opioidspossessing activity at the nociceptin receptor was determined using [H-3]nociceptin and nociceptin-stimulated [S-35]GTP gamma S binding. The mu-opioid receptor-selective agonist lofentanil potently and competitively displaced [H-3]nociceptin at rat brain receptors (IC50 62 nM). Lofentanil exhibitedfull agonism for enhancement of [S-35]GTP gamma S binding to human recombinant ORL1 receptors (EC50 50 nM). The related piperidines ohmefentanyl and sufentanil and the nonselective opioid receptor agonist etorphine were lesspotent nociceptin receptor agonists. The kappa(1) + kappa(3)-opioid receptor agonist/mu-opioid receptor antagonist naloxone benzoylhydrazone was a pure antagonist at both rat brain and human ORL1 receptors. The nonselective opioid receptor partial agonist buprenorphine and the nonselective opioid receptor antagonist (-)-quadazocine exhibited pure antagonism at rat brain receptors, but displayed partial agonism at human ORL1 receptors. Thus, opioids displaying full agonism at the nociceptin receptor are also opioid receptor agonists, whereas opioids that are antagonists or partial agonists at the nociceptin receptor show antagonism or partial agonism at opioid receptors. In addition, the stereospecificity required at opioid receptors appears to be retained at the nociceptin receptor, since (+)-quadazocine is inactive at both receptors. These findings illustrate the structural and functional homology of the opioid recognition site on these two receptor classes and suggest that opioids may provide leads for the design of nonpeptide nociceptin receptor agonists and antagonists lacking affinity for the classicalopioid receptors. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 10:26:22