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Titolo:
THE ENDOTHELIN RECEPTOR IS A MAJOR DETERMINANT FOR THE NONLINEAR TISSUE DISTRIBUTION OF THE ENDOTHELIN ANTAGONIST BQ-123
Autore:
SHIN HC; KATO Y; SHITARA Y; YAMADA T; NAKAMURA T; HISAKA A; SUGIYAMA Y;
Indirizzi:
UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU,7-3-1 HONGO TOKYO 113 JAPAN UNIV TOKYO,FAC PHARMACEUT SCI,BUNKYO KU TOKYO 113 JAPAN BANYU PHARMACEUT CO LTD,TSUKUBA RES INST TSUKUBA IBARAKI 30033 JAPAN
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 278, anno: 1996,
pagine: 607 - 613
SICI:
0022-3565(1996)278:2<607:TERIAM>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE-RENAL-FAILURE; ET(A) RECEPTOR; HYPERTENSIVE RATS; HIGHLY POTENT; SUBTYPE-A; SOMATOSTATIN; TRANSPORT; IRL-1620; AGONIST; BQ123;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
H.C. Shin et al., "THE ENDOTHELIN RECEPTOR IS A MAJOR DETERMINANT FOR THE NONLINEAR TISSUE DISTRIBUTION OF THE ENDOTHELIN ANTAGONIST BQ-123", The Journal of pharmacology and experimental therapeutics, 278(2), 1996, pp. 607-613

Abstract

The nonlinearity in the pharmacokinetics of the cyclopentapeptide endothelin antagonist BQ-123 was studied. Both the total body clearance and tissue-to-plasma concentration ratio (K-p) were investigated in rats under a wide range of steady-state plasma concentrations (C-pss) obtained by changing the intravenous infusion rate of BQ-123. The total body clearance was constant up to a C-pss level of 50 mu M, although itwas markedly decreased at higher C-pss values, which suggests the existence of a saturable elimination mechanism. A C-pss-dependent nonlinearity in the apparent K-p values (K-p,K-app) was clearly observed in many organs including lung, heart, spleen, pancreas, adrenal, stomach, intestine, colon, aorta, testis and muscle, where the endothelin ET(A)receptor is known to be localized. By fitting the saturation curves of the K-p,K-app values, a similar dissociation constant (K-d) was obtained for most organs at 5 to 10 nM, which is close to the reported K-dvalues of BQ-123 for the endothetin ET(A) receptor. The saturable portion of the K-p,K-app values observed in vivo showed a good correlation with reported values of the endothelin ET(A) receptor density. Binding of BQ-123 to isolated membrane fractions from several organs demonstrated clear saturability for the lung, heart, spleen and liver with K-d values of 1 to 3 nM. Such specific binding also showed a good correlation with the saturable portion of the K-p,K-app values. From these results, we concluded that the endothelin receptor(s) is responsible for the nonlinear tissue distribution of BQ-123 in rats.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 06:52:02