PHARMACOLOGICAL MODULATION OF ENDOTHELIN-INDUCED CONTRACTION OF GUINEA-PIG ISOLATED AIRWAYS AND THROMBOXANE RELEASE

被引:38
作者
FILEP, JG
BATTISTINI, B
SIROIS, P
机构
[1] Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec
关键词
ENDOTHELIN; THROMBOXANE RELEASE; LEUKOTRIENES; PAF; BRONCHOCONSTRICTION; ISOLATED AIRWAYS (GUINEA-PIG);
D O I
10.1111/j.1476-5381.1991.tb09840.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The aim of the present experiments was to study the possible involvement of known bronchoconstrictor substances in mediating the myotropic action of endothelin-1 (ET-1, human-porcine endothelin) in guinea-pig isolated airways. 2 ET-1 (1-100 nM) caused a dose-dependent contraction of guinea-pig trachea, upper bronchus and parenchyma. The contractions developed slowly, reaching maximal values 4-6 min after addition of the peptide. 3 The contractile action of ET-1 was significantly attenuated by indomethacin (10-mu-M), a cyclo-oxygenase blocker, BM 13505 (5-mu-M), a thromboxane receptor antagonist, FPL 55712 (19-mu-M) and YM 16638 (1-mu-M), antagonists of the sulphidopeptide leukotrienes, BN 52021 (10-mu-M) and WEB 2086 (1-mu-M), platelet-activating factor receptor antagonists in all three tissue preparations studied. 4 Pretreatment of the airway tissues with compound U 75302 (3-mu-M), a selective leukotriene B4 receptor antagonist, or with a mixture of antagonists containing methysergide (0.75-mu-M), phentolamine (0.4-mu-M), propranolol (13-mu-M), atropine (0.4-mu-M) and diphenhydramine (0.45-mu-M) did not modify the myotropic action of ET-1. 5 ET-1, 10 and 100 nM induced three, and nine fold increases in thromboxane A2 release from lung parenchymal strips. 6 ET-1-induced thromboxane A2 release was completely abolished by indomethacin, and was significantly attenuated by BN 52021, WEB 2086 and FPL 55712. Neither BM 13505 nor YM 16638 exerted a significant effect on thromboxane release. 7 The present findings show that contraction of guinea-pig airway smooth muscle by ET-1 is mediated, in part, by the release of thromboxane A2, sulphidopeptide leukotrienes and platelet-activating factor, and suggest that the increased thromboxane A2 release following ET-1 is partly a consequence of enhanced synthesis of sulphidopeptide leukotrienes and platelet-activating factor.
引用
收藏
页码:1633 / 1640
页数:8
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