COMPARISON OF PD-145065 AND RO 46-2005 AS ANTAGONISTS OF CONTRACTIONS OF GUINEA-PIG AIRWAYS INDUCED BY ENDOTHELIN-1 OR IRL-1620

被引:12
作者
BATTISTINI, B
WARNER, TD
FOURNIER, A
VANE, JR
机构
[1] ST BARTHOLOMEWS HOSP, COLL MED, WILLIAM HARVEY RES INST, LONDON EC1M 6BQ, ENGLAND
[2] INST NATL RECH SCI SANTE, MONTREAL H9R 1G6, PQ, CANADA
关键词
IRL; 1620; PD; 145065; RO; 46-2005; ENDOTHELIN ET(A)/ET(B) NONSELECTIVE RECEPTOR ANTAGONIST;
D O I
10.1016/0014-2999(94)90184-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cumulative concentrations of endothelin-1 or IRL 1620 (Suc-[Glu(9),Ala(11,15)]endothelin-1-(8-21)) an endothelin ET(B) receptor selective agonist were similarly potent in contracting guinea-pig upper bronchi, whereas endothelin-1 was more potent than IRL 1620 in contracting lung parenchymal strips. PD 145065 (10(-5) M and 10(-4) M), a non-selective endothelin ET(A)/ET(B) receptor antagonist (Ac-D-Bhg-L-Leu-L-Asp-L-Ile-L-Ile-L-Trp), significantly attenuated the contractions induced by endothelin-1 in either preparation whereas Ro 46-2005 (3 x 10(-5) M and 10(-4) M), a non-peptide non-selective receptor antagonist (4-tert-butyl-N-[6-(2-hydroxy-ethoxy)-5-3-methoxy-phenoxy)-(benzenesulfonamide)), was without effect. PD 145065 (10(-6) M and 10(-5) M) also strongly inhibited contractions induced by IRL 1620, whereas Ro 46-2005 caused much less antagonism. Thus, PD 145065 is a more potent antagonist than Ro 46-2005 of contractions induced by endothelin-1 or IRL 1620 and mediated by endothelin ET(B) receptors in these guinea-pig airway preparations.
引用
收藏
页码:341 / 345
页数:5
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