Dibutyryl cyclic guanosine monophosphate elevates bovine endothelial cell thromboxane production without affecting prostacyclin metabolism.
Cloned bovine aortic endothelial cells (BAEC) were grown to confluence then treated for 24 hours with dibutyryl cyclic AMP (dbcAMP) or dibutyryl cyclic GMP (dbcGMP) in serum free medium. Submillimolar concentrations of dbcGMP caused a significant enhancement of thromboxane (TXB2) synthesis in washed cells exposed to arachidonate. DbcAMP had no effect on the production of either metabolite. TXB2 synthesis was inhibited by 3 micrograms/ml cycloheximide, whether or not the cells were pretreated with dbcGMP. Prostacyclin production was inhibited to a much lesser extent by cycloheximide. We conclude that dbcGMP elevates TXB2 production by increasing the amount of thromboxane synthetase available, and that this effect is inhibited by cycloheximide. Data are described which suggest that dbcGMP increases the degradation rate of TXB2 by BAEC, so that the observed increase in TXB2 may be an underestimate of the true effects of dbcGMP on TXB2 production.
D000818:Animals; D001011:Aorta / Q000166:cytology; D003994:Bucladesine / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives*; D003513:Cycloheximide / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004727:Endothelium / Q000166:cytology; D011464:Epoprostenol / Q000378:metabolism*; D066298:In Vitro Techniques; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000378:metabolism; D013931:Thromboxanes / Q000096:biosynthesis*
D013931:Thromboxanes; D003995:Dibutyryl Cyclic GMP; D013929:Thromboxane B2; D003994:Bucladesine; D003513:Cycloheximide; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D006152:Cyclic GMP