Mechanism of increased angiotensin-converting enzyme activity stimulated by platelet-activating factor.
We studied the effects of platelet activating factor (PAF) on angiotensin-converting enzyme (ACE). PAF (1 x 10(-10) to 1 x 10(-6) M) had a novel effect on angiotensin I conversion. Pulmonary artery endothelial cells converted 1 nmol/dish of 125I-angiotensin I to angiotensin II in the absence of PAF. ACE activity was increased to 2.5 nmol/dish by the addition of 1 x 10(-6) M of PAF. To clarify the mechanism of this stimulatory effect of PAF on ACE, Ca2+ influx and inositol 1,4,5-trisphosphate (IP3) release in pulmonary artery endothelial cells were determined. PAF stimulated Ca2+ influx in a dose-dependent manner. PAF also stimulated phospholipase C (PLC) activity and released IP3. To study the relationship between PLC activity and ACE activity, neomycin was added. The Ca2+ influx and IP3 release stimulated by 10(-6) M of PAF were suppressed by about 60-70%. ACE activity was also inhibited up to 70% in the presence of PAF (10(-10) - 10(-6) M) by 50 M of neomycin. These results suggest that ACE was stimulated by PAF, and that its activity in endothelial cells may be mediated by the PI-turnover pathway via changes in PLC activity and IP3-mediated Ca2+ release from intracellular stores.
Kawaguchi
H
H
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Sawa
H
H
Yasuda
H
H
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000187:drug effects / Q000201:enzymology; D009355:Neomycin / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism
D010972:Platelet Activating Factor; D000804:Angiotensin II; D000803:Angiotensin I; D010738:Type C Phospholipases; D007703:Peptidyl-Dipeptidase A; D009355:Neomycin; D002118:Calcium