Selective inhibition by minoxidil of prostacyclin production by cells in culture.
The effect of minoxidil on arachidonic acid metabolism by cells in culture was studied. In bovine aorta endothelial cells, treatment with minoxidil in the presence of various stimulators of arachidonic acid metabolism was accompanied by a dose-dependent inhibition of prostacyclin production (measured as 6-keto-prostaglandin F1 alpha). Synthesis of the other cyclooxygenase products (prostaglandins E2, F2 alpha and thromboxane) was not inhibited. When the bovine aorta endothelial cells were stimulated by the Ca2+ ionophore A-23187, the inhibition was seen as early as 2 min. Minoxidil also inhibited prostacyclin production by a second cell line of bovine aorta endothelial cells (the established CPAE cell line), bovine aorta smooth muscle cells, porcine aorta endothelial cells, and rat liver cells (the C-9 cell line)--the latter, less effectively. Again, formation of all the other cyclooxygenase products studied was not inhibited. Minoxidil did not affect significantly prostaglandin E2 and F2 alpha production by newborn rat keratinocytes (the NBR cell line)--a cell that does not produce PGI2. The clinical, biochemical, and pharmacologic implications are discussed.
Kvedar
J C
JC
Department of Biochemistry, Brandeis University, Waltham, MA 02254.
Baden
H P
HP
Levine
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D015237:Dinoprost; D015232:Dinoprostone; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D008555:Melitten / Q000494:pharmacology; D008914:Minoxidil / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis; D011460:Prostaglandins F / Q000096:biosynthesis; D011863:Radioimmunoassay; D022603:Shiga Toxins
D001427:Bacterial Toxins; D011458:Prostaglandins E; D011460:Prostaglandins F; D022603:Shiga Toxins; D008555:Melitten; D015121:6-Ketoprostaglandin F1 alpha; D008914:Minoxidil; D015237:Dinoprost; D011464:Epoprostenol; D015232:Dinoprostone; D001920:Bradykinin