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Titolo:
Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist
Autore:
Skuladottir, GV; Jonsson, L; Skarphedinsson, JO; Mutulis, F; Muceniece, R; Raine, A; Mutule, I; Helgason, J; Prusis, P; Wikberg, JES; Schioth, HB;
Indirizzi:
UppsalanUniv, Biomed Ctr, Dept Pharmaceut Pharmacol, S-75124 Uppsala, Swede Uppsala Univ Uppsala Sweden S-75124 ut Pharmacol, S-75124 Uppsala, Swede Univ Iceland, Dept Physiol, IS-101 Reykjavik, Iceland Univ Iceland Reykjavik Iceland IS-101 Physiol, IS-101 Reykjavik, Iceland Inst Organ Synth, Dept Med Chem, LV-1006 Riga, Latvia Inst Organ Synth Riga Latvia LV-1006 Dept Med Chem, LV-1006 Riga, Latvia Inst Organ Synth, Pharmacol Lab, LV-1006 Riga, Latvia Inst Organ Synth Riga Latvia LV-1006 Pharmacol Lab, LV-1006 Riga, Latvia
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 126, anno: 1999,
pagine: 27 - 34
SICI:
0007-1188(199901)126:1<27:LTOEOA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOLECULAR-CLONING; RADIOLIGAND BINDING; ALPHA-MELANOTROPIN; ANALOGS; IDENTIFICATION; LOCALIZATION; EXPRESSION; PEPTIDES; SUBTYPES; HORMONE;
Keywords:
melanocortin (MC) receptor subtypes; MSH (melanocyte stimulating hormone); ligand binding; cyclic AMP; HS028; chronic icv administration; food intake;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Schioth, HB Uppsalala,iv, Biomed Ctr, Dept Pharmaceut Pharmacol, Box 591, S-75124 Uppsa Uppsala Univ Box 591 Uppsala Sweden S-75124 91, S-75124 Uppsa
Citazione:
G.V. Skuladottir et al., "Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist", BR J PHARM, 126(1), 1999, pp. 27-34

Abstract

1 We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors.2 One of the substances HS028 (cyclic [AcCys(11), dichloro-D-phenylalanine(14), Cys(18), Asp-NH222]-beta-MSH11-22) showed high affinity (Ki of 0.95 nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014.3 HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors.4 Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight ina dose dependent manner without tachyphylaxis for a period of 7 days.5 This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 20:58:28