THROMBOSIS RESEARCH 42; 383-396, 1986 0049-3848/86 $3.00 t .OO Printed in the USA. Copyright (c) 1986 Pergamon Press Ltd. All rights reserved. HPPHCISCFPHoRBoaDlESIERSAND TELEXIDINCNNORMALHUMANPLATEIlETS F&r tech, Michael H. Rosove, Sylvia S. L. Harwig, andRcbert1.Lehrer* Division of Hematology and Onc&qy Department of Medicine UCIAScfioolof Medicine The CenterfortheHealth Sciences Ios Angeles, California 90024 * armiVA Medical Center, We&Los Angeles, CA 90073, U.S.A. (Received 1.6.1985; Accepted in revised form2.8.1985 by Editor J.G.White) (Received in final form by Executive Editorial Office18.2.1986) Teleocidins are newlydescribed indole alkaloid tumor promoters thatare structurally distinct franphorbol diesters (PDE). We canpared the effects of teleocidin and selected PDE cn platelet aggregation, secretionard aspects of arachidonate metabolism. Three t-r-lpanoting PDE (phorbolmyristate acetate (PMA), phorbol dibutyrate (PDHu) and 4-Bphorboldidecanoa te (I-6-PDD)) and a non-tumor prxxmoting PDE (4-a-phorizol didecanoate (4-cl_PDD)) were used. Teleocidin ti tumorpromoting PDE caused platelet aggregation after adelaythatwas inversely related to tumor pm&x.r concentration and alsotriggered secretionof a- and dense granules and selectiverelme of lysosanalenzymes. Aggregation and its associated I-fibrinogen binding to platelets were both inhibitedby Na2EDIA. 4-a-PDD was ineffective. Analysis of platelet aggregation responsesand activationkinetics revealed thatPDHuwas 11.7 times less potent than teleocidif4 PMA, or 4-B-PDD. Neither PDE nor teleccidinstimulated C-arachitite release fromnormal human platelets,and bothaggregated aspirin-treated platelets.These results show thatrepresentatives of two structurally distinct classes of twror pranoters, phorbol diesters and irxdole alkaloids, are potent activatorsof platelet aggregation, fibrinogenbinding, and granule/lysoscrml secretion, by a mechanisn that bypassesarachidcnatereleaseand formationof cyclooxygenase-dependent arachidonate metabolites. Key Words: cyclooxygenase, platelets, teleocidin, tumorprceoters 383