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Titolo:
Effects of YM471, a nonpeptide AVP V-1A and V-2 receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells
Autore:
Tsukada, J; Tahara, A; Tomura, Y; Wada, K; Kusayama, T; Ishii, N; Yatsu, T; Uchida, W; Taniguchi, N; Tanaka, A;
Indirizzi:
Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Tsukuba, Ibaraki 3058585, Japan Yamanouchi Pharmaceut Co Ltd Tsukuba Ibaraki Japan 3058585 3058585, Japan
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 5, volume: 133, anno: 2001,
pagine: 746 - 754
SICI:
0007-1188(200107)133:5<746:EOYANA>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
ARGININE-VASOPRESSIN ANTAGONISTS; PHARMACOLOGICAL CHARACTERIZATION; HIGHLY POTENT; MOLECULAR-CLONING; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; RAT; BINDING; YM087; V2-RECEPTOR;
Keywords:
human vasopressin receptors; antagonist; YM471; SR 49059; SR 121463A;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Tahara, A Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, 21 Miyyktsukuba, Tsukuba, Ibaraki 3058585, Japan Yamanouchi Pharmaceut Co Ltd 21 Miyyktsukuba Tsukuba Ibaraki Japan 3058585
Citazione:
J. Tsukada et al., "Effects of YM471, a nonpeptide AVP V-1A and V-2 receptor antagonist, on human AVP receptor subtypes expressed in CHO cells and oxytocin receptors in human uterine smooth muscle cells", BR J PHARM, 133(5), 2001, pp. 746-754

Abstract

1 YM471, (Z)-4'-{4,4-difluoro-5-[2-(4-dimethylaminopiperidino)-2-oxoethylidene]-2,3,4,5-tetrahydro-1H-1-benzoazepine-1-carbonyl}-2-phenylbenzanilide monohydrochloride, is a newly synthesized potent vasopressin (AVP) receptorantagonist. Its effects on binding to and signal transduction by cloned human AVP receptors (V-1A, V-1B and V-2) stably expressed in Chinese hamster ovary (CHO) cells, and oxytocin receptors in human uterine smooth muscle cells (USMC) were studied.2 YM471 potently inhibited specific [H-3]-AVP binding to V-1A and V-2 receptors with K-i values of 0.62 nhl and 1.19 nM, respectively. In contrast, YM471 exhibited much lower affinity for V-1B and oxytocin receptors with K-ivalues of 16.4 muM and 31.6 nM, respectively.3 In CHO cells expressing V-1A receptors, YM471 potently inhibited AVP-induced intracellular Ca2+ concentration ([Ca2+](i)) increase, exhibiting an IC50 value of 0.56 nM. However, in human USMC expressing oxytocin receptors,YM471 exhibited much lower potency in inhibiting oxytocin-induced [Ca2+](i) increase (IC50 = 193 nM), and did not affect AVP-induced [Ca2+](i) increase in CI-IO cells expressing VIE receptors. Furthermore, in CHO cells expressing Vt receptors, YM471 potently inhibited the production of cyclic AMP stimulated by AVP with an IC50 value of 1.88 nhl. In all assays, YM471 showed no agonistic activity.4 These results demonstrate that YM471 is a potent, nonpeptide human VIA and Vt receptor antagonist which will be a valuable tool in defining the physiologic and pharmacologic actions of AVP.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 13:21:48