Vol. 177, No. 1, 1991 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS May 31, 1991 Pages 171-176 ENDOTHELIN-1 tNDUCES PROSTACYCLIN RELEASE FROM BOVINE AORTIC ENDOTHELIAL CELLS Janos G. Filep l*, Bruno Battistini I, Yvan P. C&e *, Adrien R. Beaudoin * and Pierre Sirois 1 Departments of 1 Pharmacology and * Biology, Faculty of Medicine, University of Sherbrooke, Sherbrooke, P.Q., Canada JlH 5N4 Received March 27, 1991 SUMMARY: The effects of endothelin-1 (ET-l) on the release of prostacyclin from cultured bovine aortic endothelial cells were studied. ET-l induced a time- and dose-dependent release of 6-keto PGF,,, the stable metabolite of prostacyclin, with an apparent EC,, value of 3.0 kO.9 nM (n=6). ET-l up to a concentration of 500 nM did not affect cellular integrity. Preincubation of the cells for 30 min with 10 FM indomethacin inhibited ET-l (100 nM) - induced prostacyclin release by 90 % . These findings indicate that ET-l can directly stimulate prostacyclin release from endothelial cells probably through a receptor mediated mechanism. 0 1991 Academic Press. Inc. Endothelin-1 (ET-l) first isolated from conditioned medium of cultured vascular endothelial cells (1) is now well characterized as a potent constrictor of vascular and non-vascular smooth muscles both in vivo and in vitro (c.f. 2). In addition to its contractile action, ET-l has been shown to inhibit ex vivo aggregation of rabbit platelets (3) as well as in vivo platelet aggregation in the dog (4) and rabbit (5), whereas it has no effect on in vitro platelet aggregation (3,4). Since indomethacin and aspirin can block the antiaggregatory action of ET-l, the involvement of an antiaggregatory cyclooxygenase product, presumably prostacyclin, has been suggested (3,4). This view is further supported by the findings that the in vivo anti aggregatory action of ET-l in the dog was accompanied by enhanced plasma levels of 6-keto PGF,,, the hydrolytic metabolite of prostacyclin (4). The present experiments were designed to study the effects of ET-l on prostacyclin release from monolayer * To whom correspondence should be addressed. 0006-291X/91 $1.50 171 Copyight 0 1991 by Academic Press, Inc. AlI rights of reproduction in any form reserved.