Calcium ionophore A23187 elevates angiotensin-converting enzyme in cultured bovine endothelial cells.
Calcium ionophore A23187 (0.3-0.4 microM) elevated cellular angiotensin-converting enzyme activity (ACE) 2-7-fold after 48 h incubation with bovine pulmonary artery endothelial cells in culture. Cycloheximide (0.1 micrograms/ml) blocked the elevation in ACE produced by A23187. The increase in ACE was inhibited by 0.2 mM EGTA, 50 microM verapamil and 50 microM nifedipine, and was not associated with changes in cellular cAMP. Melittin, a phospholipase A2 activator, or addition of exogenous arachidonic acid failed to reproduce the elevation, and indomethacin only partially blocked the A23187 effect. The elevation of ACE was also inhibited by the calcium-calmodulin inhibitor, calmidazolium. Thus, we postulate that the ionophore A23187 elevates ACE in endothelial cells through a calcium-dependent mechanism other than phospholipase A2 activation. The elevation depends on new protein synthesis and involves calcium-calmodulin-dependent cellular mechanisms.
Dasarathy
Y
Y
New England Medical Center Hospital, Pulmonary Division, Boston, MA 02111.
Fanburg
B L
BL
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D007093:Imidazoles / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D007093:Imidazoles; D000001:Calcimycin; C031938:calmidazolium; D004533:Egtazic Acid; D003513:Cycloheximide; D014700:Verapamil; D000242:Cyclic AMP; D007703:Peptidyl-Dipeptidase A; D009543:Nifedipine