THE SELECTIVE ENDOTHELIN ET(A) RECEPTOR ANTAGONIST BQ123 ANTAGONIZES ENDOTHELIN-1-MEDIATED MITOGENESIS

被引：159

作者：

OHLSTEIN, EH

ARLETH, A

BRYAN, H

ELLIOTT, JD

SUNG, CP

机构：

[1] SMITHKLINE BEECHAM PHARMACEUT,DEPT PEPTIDOMIMET RES,KING OF PRUSSIA,PA 19406

[2] SMITHKLINE BEECHAM PHARMACEUT,DEPT PHARMACOL,KING OF PRUSSIA,PA 19406

[3] SMITHKLINE BEECHAM PHARMACEUT,DEPT MED CHEM,KING OF PRUSSIA,PA 19406

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1992年 / 225卷 / 04期

关键词：

ENDOTHELIN; MITOGENESIS; ENDOTHELIN ET(A) RECEPTOR; ENDOTHELIN ET(B) RECEPTOR; BQ123;

D O I：

10.1016/0922-4106(92)90109-9

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The mitogenic effects of endothelin isopeptides and the selective ET(A) receptor antagonist BQ123 were evaluated in rat aortic vascular smooth muscle cells. Endothelin-1 (ET-1) and endothelin-3 (ET-3) produced concentration-dependent increases in [H-3]thymidine incorporation (EC50 = 0.1 and 25 nM, respectively). The ET(B)-selective agonist sarafotoxin 6c did not produce significant effects on [H-3]thymidine incorporation. BQ123 produced selective and concentration-dependent inhibition of ET-1-mediated [H-3]thymidine incorporation. These data demonstrate that ET-1-mediated mitogenesis in vascular smooth muscle is mediated by ET(A) receptors.

引用

收藏

页码：347 / 350

页数：4

相关论文

共 11 条

[1] CLONING AND EXPRESSION OF A CDNA-ENCODING AN ENDOTHELIN RECEPTOR [J].

ARAI, H ;

HORI, S ;

ARAMORI, I ;

OHKUBO, H ;

NAKANISHI, S .

NATURE, 1990, 348 (6303) :730-732

[2]

FUKAMI T, 1991, 12TH AM PEPT S CAMBR, P506

[3]

HILEY CR, 1992, IN PRESS BR J PHARM

[4] THE HUMAN ENDOTHELIN FAMILY - 3 STRUCTURALLY AND PHARMACOLOGICALLY DISTINCT ISOPEPTIDES PREDICTED BY 3 SEPARATE GENES [J].

INOUE, A ;

YANAGISAWA, M ;

KIMURA, S ;

KASUYA, Y ;

MIYAUCHI, T ;

GOTO, K ;

MASAKI, T .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2863-2867

[5] ENDOTHELIN STIMULATES C-FOS AND C-MYC EXPRESSION AND PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS [J].

KOMURO, I ;

KURIHARA, H ;

SUGIYAMA, T ;

TAKAKU, F ;

YAZAKI, Y .

FEBS LETTERS, 1988, 238 (02) :249-252

[6] CIRCULATING AND TISSUE ENDOTHELIN IMMUNOREACTIVITY IN ADVANCED ATHEROSCLEROSIS [J].

LERMAN, A ;

EDWARDS, BS ;

HALLETT, JW ;

HEUBLEIN, DM ;

SANDBERG, SM ;

BURNETT, JC .

NEW ENGLAND JOURNAL OF MEDICINE, 1991, 325 (14) :997-1001

[7] PLATELETS STIMULATE EXPRESSION OF ENDOTHELIN MESSENGER-RNA AND ENDOTHELIN BIOSYNTHESIS IN CULTURED ENDOTHELIAL-CELLS [J].

OHLSTEIN, EH ;

STORER, BL ;

BUTCHER, JA ;

DEBOUCK, C ;

FEUERSTEIN, G .

CIRCULATION RESEARCH, 1991, 69 (03) :832-841

[8] CLONING OF A CDNA-ENCODING A NON-ISOPEPTIDE-SELECTIVE SUBTYPE OF THE ENDOTHELIN RECEPTOR [J].

SAKURAI, T ;

YANAGISAWA, M ;

TAKUWA, Y ;

MIYAZAKI, H ;

KIMURA, S ;

GOTO, K ;

MASAKI, T .

NATURE, 1990, 348 (6303) :732-735

[9] ENDOTHELIN STIMULATES PHOSPHOLIPASE-C, NA+/H+ EXCHANGE, C-FOS EXPRESSION, AND MITOGENESIS IN RAT MESANGIAL CELLS [J].

SIMONSON, MS ;

WANN, S ;

MENE, P ;

DUBYAK, GR ;

KESTER, M ;

NAKAZATO, Y ;

SEDOR, JR ;

DUNN, MJ .

JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (02) :708-712

[10] SARAFOTOXIN-S6C - AN AGONIST WHICH DISTINGUISHES BETWEEN ENDOTHELIN RECEPTOR SUBTYPES [J].

WILLIAMS, DL ;

JONES, KL ;

PETTIBONE, DJ ;

LIS, EV ;

CLINESCHMIDT, BV .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 175 (02) :556-561