Mechanism of increased angiotensin-converting enzyme activity stimulated by platelet-activating factor

Abstract

We studied the effects of platelet activating factor (PAF) on angiotensin-converting enzyme (ACE). PAF (1 · 10 −10 to 1 · 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 · 10 −6 M of PAF. To clarify the mechanism of this stimulatory effect of PAF on ACE, Ca 2+ influx and inositol 1,4,5-trisphosphate (IP 3) release in pulmonary artery endothelial cells were determined. PAF stimulated Ca 2+ influx in a dose-dependent manner. PAF also stimulated phospholipase C (PLC) activity and released IP 3. To study the relationship between PLC activity and ACE activity, neomycin was added. The Ca 2+ influx and IP 3 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 activityl in endothelial cells may be mediated by the PI-turnover pathway via changes in PLC activity and IP 3-mediated Ca 2+ release from intracellular stores.