Printed i USA. ABSTRACT Tus Jouaw. or PHARMACOLOGY AND EXPnuuENTAL Tiimreuncs Copyright C 1990by Th. American Society for Pharmacology and Experimental Therapeutics Selective Inhibition of Receptor-Coupled Phospholipase C- Dependent Processes in Human Pl

Aggregation of human platelets indUCed by a variety of agonists was inhibited by I-[6-{[1 7-3-methoxyestra-1,3,5(1 0)-then-I 7-yl] amino)hexyl]-1 H-pyrrole-2,5-dione (11-73122) (ICso V8JU88 1-5 gM), but not by the close analog 1-[6-[[17fi-3-methoxyestra-1,3,5(1 0)-then-i 7-yljamino]hexylJ-2,5-pyrrolidine-dione(U-73343) in which pyrrinsdione was substftuted for pyrroindione. Inhi-bition by U-731 22 was not mediated by an increase in intracellular cyclic AMP. In contrast, the production of inositol 1,4,5-trisphos-phate (1P3) and the subsequent rapid increase in CYtOSOIIC Ca ’ induced by efther thrombin or the thromboxane-mimec, (5Z,9a, 1 1 a, 1 3E,1 55)1 5-hydroxy-1 I,9-(epoxymethano)prosta-5,13,-dien-1-oic acid (11-46619), was inhibited by U-73122 bu