Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Structure-activity studies on nociceptin/orphanin FQ: from full agonist, to partial agonist, to pure antagonist
Autore:
Salvadori, S; Guerrini, R; Calo, G; Regoli, D;
Indirizzi:
Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy Univ Ferrara Ferrara Italy I-44100 harmaceut Sci, I-44100 Ferrara, Italy Univ Ferrara, Dept Expt & Clin Med, Pharmacol Sect, I-44100 Ferrara, ItalyUniv Ferrara Ferrara Italy I-44100 harmacol Sect, I-44100 Ferrara, Italy
Titolo Testata:
FARMACO
fascicolo: 11-12, volume: 54, anno: 1999,
pagine: 810 - 825
SICI:
0014-827X(199911/12)54:11-12<810:SSONFF>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-COUPLED RECEPTORS; MOUSE VAS-DEFERENS; ORPHAN OPIOID RECEPTOR; RAT SPINAL-CORD; IN-VITRO; TISSUE DISTRIBUTION; MOLECULAR-CLONING; ORL1 RECEPTOR; GENE FAMILY; GUANYLYL-5'-O-(GAMMA-THIO)-TRIPHOSPHATE BINDING;
Keywords:
nociceptin; orphanin FQ; nociceptin analogs; OP4; bioassay; mouse vas deferens; receptor binding;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
117
Recensione:
Indirizzi per estratti:
Indirizzo: Salvadori, S Univ Ferrara, Dept Pharmaceut Sci, Via Fossato Mortara 17-19,I-44100 Ferrara, Italy Univ Ferrara Via Fossato Mortara 17-19 Ferrara Italy I-44100
Citazione:
S. Salvadori et al., "Structure-activity studies on nociceptin/orphanin FQ: from full agonist, to partial agonist, to pure antagonist", FARMACO, 54(11-12), 1999, pp. 810-825

Abstract

A heptadecapeptide (Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Asn-Gln) was identified from rat brain and from porcine brain as a ligand for OP4, a new G-protein coupled receptor that is similar in sequence to opioid receptors. The OP4 receptor is widely expressed in the nervous system where it mediates a broad range of physiological functions. The new peptide, nociceptin (NC), has a primary sequence recalling that of opioid peptides. Despite the homologies (a) of the OP4 receptor with known opioid receptors, especially the OP2 (kappa) receptor, and (b) of NC with opioid peptides, particularly dynorphin A, the two biological systems have different anatomical locations and chemical requirements for activation. NC does not bind to opioid receptors, and mammalian opioid peptides do not interact with the OP4 receptor. The presence of Phe in position 1 and Arg in position 8, appear to be instrumental to exclude NC from interacting with the opioid receptors. Contrary to opioid peptides which strikly require Tyr in position 1, the active core that activates the OP4 appears to be towards the centre of the peptide molecule and includes Phe(4). Based on the message/address model, several changes have been made in the N-terminal tetrapeptide Phe-Gly-Gly-Phe (message)and a few also in the C-terminal of the template NC(1-13)-NH2, a fragment that acts as a full agonist both in vitro and in vivo. Subtle changes of the N-terminal sequence, especially at Phe(1), led to the discovery of peptide antagonists ([Phe(1)Psi(CH2-NH)Gly(2)]-NC(1-13)-NH2 and [Nphe(1)]-NC(1-13)-NH2). The first compound has been widely used to characterize NC actions in the periphery and in the central nervous system. It has been shown to act mainly as an antagonist outside the brain and as an agonist in the central nervous system. [Nphe(1)]-NC(1-13)-NH2 on the contrary, acts as antagonist both in the periphery and in the brain. These first peptide prototypes may soon be followed by non-peptide compounds, some of which, are already described in patent literature. (C) 1999 Elsevier Science S.A. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 31/03/20 alle ore 18:45:33