title: Drug stimulated prostacyclin release.
abstract: We suggest pentoxifylline (POF) to exert in vivo its offiaggregatory effect by enhancing prostacyclin (PGI2)-like activity from the vessel walls, which in turn stimulates platelet adenylate cyclase resulting in an elevated cyclic AMP level in the platelets. Despite its inhibitory effect on platelet cAMP phosphodiesterase, POF without PGI2 has almost no effect in vitro on cAMP levels in human platelets or on the inhibition of aggregation. However, a combination of POF together with PGI2 in these in vitro systems drastically stimulates cAMP-levels as well as inhibition of aggregation above that concerning to PGI2 itself. We therefore conclude that the intact vessel wall-platelet interaction is required for the anti-aggregatory action of POF in vivo.
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D010431:Pentoxifylline / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000031:analogs & derivatives*
chemical_list: D011464:Epoprostenol; D000242:Cyclic AMP; D013805:Theobromine; D010431:Pentoxifylline