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Titolo:
Distinct mechanisms for activation of the opioid receptor-like 1 and kappa-opioid receptors by nociceptin and dynorphin A
Autore:
Mollereau, C; Mouledous, L; Lapalu, S; Cambois, G; Moisand, C; Butour, JL; Meunier, JC;
Indirizzi:
CNRS, Inst Pharmacol & Biol Struct, F-31077 Toulouse, France CNRS Toulouse France F-31077 col & Biol Struct, F-31077 Toulouse, France
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 2, volume: 55, anno: 1999,
pagine: 324 - 331
SICI:
0026-895X(199902)55:2<324:DMFAOT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
NEUROPEPTIDE ORPHANIN FQ; 2ND EXTRACELLULAR LOOP; TISSUE DISTRIBUTION; ORL(1) RECEPTOR; ORL1 RECEPTOR; BINDING; LIGAND; PEPTIDE; RAT; RECOGNITION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Meunier, JC CNRS,ulouse,harmacol & Biol Struct, UPR 9062,205 Route Narbonne, F-31077 To CNRS UPR 9062,205 Route Narbonne Toulouse France F-31077 7 To
Citazione:
C. Mollereau et al., "Distinct mechanisms for activation of the opioid receptor-like 1 and kappa-opioid receptors by nociceptin and dynorphin A", MOLEC PHARM, 55(2), 1999, pp. 324-331

Abstract

To understand how two structurally analogous ligand-receptor systems, the nociceptin/opioid receptor-like 1 (ORL1) and dynorphin A/kappa-opioid receptor 1 (KOR1) systems, achieve selectivity, receptor chimeras were generatedand analyzed. Replacing discrete domains located between the N-terminus and top of the third transmembrane helix of the KOR1 by the homologous domains of the ORL1 receptor yields hybrid receptors, which, in comparison with the parent KOR1, display up to 300-fold increased affinity but low sensitivity toward nociceptin, and unaltered (high) affinity and sensitivity toward dynorphin A. These substitutions contribute elements for binding of nociceptin but do not suppress determinants necessary for binding and potency of dynorphin A. More importantly, further replacement in these chimeras of the second extracellular loop with that of the ORL1 receptor fully restores responsiveness to nociceptin without impairing responsiveness to dynorphin A. A bifunctional hybrid receptor has thus been identified that binds and responds to both nociceptin and dynorphin A as efficiently as the ORL1 receptordoes to nociceptin and the KOR1 to dynorphin A. Together, these results suggest that distinct peptide activation mechanisms operate in the two receptor systems. In particular, the second extracellular receptor loop appears to be an absolute requirement for activation of the ORL1 receptor by nociceptin, but not for activation of the KOR1 by dynorphin A.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 13:12:31