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Titolo:
EFFECTS OF RECOMBINANT AGOUTI-SIGNALING PROTEIN ON MELANOCORTIN ACTION
Autore:
YANG YK; OLLMANN MM; WILSON BD; DICKINSON C; YAMADA T; BARSH GS; GANTZ I;
Indirizzi:
6504 MSRBI,1150 W MED CTR DR ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT INTERNAL MED ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT PEDIAT ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT PHYSIOL ANN ARBOR MI 48109 UNIV MICHIGAN,DEPT SURG ANN ARBOR MI 48109 STANFORD UNIV,HOWARD HUGHES MED INST STANFORD CA 94305 STANFORD UNIV,DEPT PEDIAT STANFORD CA 94305 STANFORD UNIV,DEPT GENET STANFORD CA 94305
Titolo Testata:
Molecular endocrinology
fascicolo: 3, volume: 11, anno: 1997,
pagine: 274 - 280
SICI:
0888-8809(1997)11:3<274:EORAPO>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
MELANOCYTE-STIMULATING-HORMONE; MOLECULAR-CLONING; HUMAN HOMOLOG; CELL-LINE; GENE; EXPRESSION; RECEPTOR; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
Y.K. Yang et al., "EFFECTS OF RECOMBINANT AGOUTI-SIGNALING PROTEIN ON MELANOCORTIN ACTION", Molecular endocrinology, 11(3), 1997, pp. 274-280

Abstract

Mouse agouti protein is a paracrine signaling molecule that has previously been demonstrated to be an antagonist of melanocortin action at several cloned rodent and human melanocortin receptors. In this study we report the effects of agouti-signaling protein (ASIP), the human homolog of mouse agouti, on the action of alpha-MSH or ACTH at the five known human melanocortin receptor subtypes (hMCR 1-5). When stably expressed in L cells (hMC1R, hMC3R, hMC4R, hMC5R) or in the adrenocortical cell line OS3 (hMC1R, hMC2R, hMC4R), purified recombinant ASIP inhibits the generation of cAMP stimulated by alpha-MSH (hMC1R, hMC3R, hMC4R, hMC5R) or by ACTH (hMC2R). However, dose-response and Schild analysis indicated that the degree of ASIP inhibition varied significantly among the receptor subtypes; ASIP is a potent inhibitor of the hMC1R, hMC2R, and hMC4R, but has relatively weak effects at the hMC3R and hMC5R. These analyses also indicated that the apparent mechanism of ASIP antagonism varied among receptor subtypes, with characteristics consistent with competitive antagonism observed only at the hMC1R, and more complex behavior observed at the other receptors. ASIP inhibition at these latter receptors, nonetheless, can be classified as surmountable (hMC3R, hMC4R and hMC5R) or nonsurmountable (hMC2R). Recombinant ASIP also inhibited binding of radiolabeled melanocortins, [I-125-Nle(4), D-Phe(7)]alpha-MSH and [I-125-Phe2(,) Nle(4)]ACTH 1-24, to the hMCR 1-5 receptors, with a relative efficacy that paralleled the ability of ASIP to inhibit cAMP accumulation at the hMC1R, hMC2R, hMC3R, and hMC4R. These results provide new insight into the biochemical mechanism of ASIP action and suggest that ASIP may play an important role in modulating melanocortin signaling in humans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/09/20 alle ore 11:49:25