Effects of pharmacological and physiological modulators on Ca-ATPase and alkaline phosphatase activities from guinea-pig placenta in vitro.

In a search for modulators of Ca-ATPase and AP activities, we examined three pharmacological agents and the cations Ca2+ and Zn2+. Placental Ca-ATPase specific activity was uncompetitively inhibited in vitro by millimolar concentrations of the diuretics ethacrynic acid and furosemide. Cysteine, a sulphydryl donor, partially reversed the ethacrynic acid inhibition but enhanced the furosemide inhibition, indicating that sulphydryl-binding may be part of the mechanism of the inhibition of Ca-ATPase by ethacrynic acid but not by furosemide. In contrast to Ca-ATPase, AP activity was enhanced by both ethacrynic acid and furosemide. Zinc inhibited Ca-ATPase activity at all concentrations tested, but enhanced and, at higher concentrations, inhibited AP activity. The inhibition of AP activity by D-penicillamine was reversed by Zn, supporting the view that this drug acts by chelating Zn which is essential for AP activity. D-penicillamine had no significant effect on Ca-ATPase activity. Calcium activated both enzyme activities but inhibited only AP activity at higher concentrations. These results indicate that placental Ca-ATPase and AP activities may be distinct and dissociable based on responses to various pharmacological and physiological modulators.