Inhibitory action of cilostazol, a phosphodiesterase III inhibitor, on catecholamine secretion from cultured bovine adrenal chromaffin cells.
The effect of cilostazol, a phosphodiesterase III inhibitor, on catecholamine secretion was examined using bovine adrenal chromaffin cells in culture. Catecholamine secretion evoked by acetylcholine was markedly inhibited by cilostazol. In contrast, 56 mM K+-evoked secretion was slightly inhibited by cilostazol. Cilostazol elevated the level of cyclic AMP in the cells. However, a cyclic AMP analog (dibutyryl cAMP) or an adenylate cyclase activator (forskolin) failed to inhibit secretion of catecholamine induced by acetylcholine. Cilostazol decreased the level of intracellular free Ca2+ stimulated by acetylcholine. Cilostazol thus inhibits secretion of catecholamine through its blocking action on Ca2+ movement in the adrenal chromaffin cells.
Azuma
Mami
M
Department of Pharmacy, Tokushima University Hospital, Tokushima, Japan.
Houchi
Hitoshi
H
Mizuta
Makiko
M
Kinoshita
Masahiro
M
Teraoka
Kazuhiko
K
Minakuchi
Kazuo
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000313:Adrenal Medulla / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*
D002395:Catecholamines; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol