ENDOTHELIN-1 STIMULATES CYTOSOLIC PHOSPHOLIPASE A(2), IN CHINESE-HAMSTER OVARY CELLS STABLY EXPRESSING THE HUMAN ET(A) OR ET(B) RECEPTOR SUBTYPE

The ability of endothelin-1 (ET-1) to activate cytosolic phospholipase A(2) (cPLA(2)) has been studied in Chinese Hamster ovary (CHO) cells stably expressing either the human ET(A) (CHO/ET(A)) or the human ET(B) (CHO/ET(B)) receptor subtype. ET-1 dose-dependently increased a dithiothreitol-insensitive cPLA(2) activity in both cell types. In CHO/ET(A) cells, BQ-123, an ET(A)-selective antagonist, completely blocked ET-1-induced cPLA(2) stimulation. In CHO/ET(B) cells, the ET-1 response was mimicked by 4AlaET-1 which could be blocked partially by PD 145065, a nonselective antagonist of ET(A) and ET(B). As expected, ET-1 stimulated PGE(2) synthesis in CHO cells transfected with ET receptors. We conclude that ET-1 can stimulate cPLA(2) via both the human ET(A) and ET(B) receptor subtype. (C) 1994 Academic Press, Inc.