Effects of prostacyclin and prostaglandin E1 on cyclic AMP metabolism and calcium efflux in isolated renal cortical tubules

Abstract

Comparative effects of prostaglandin E1 (PGE1) prostacyclin (PGI2) on cyclic AMP (cAMP) metabolism and efflux of 45Ca in isolated renal cortical tubules from hamsters were investigated. Both PGE1 and PGI2 increased tissue concentrations and production of cAMP in isolated tubules with effects of PGE1 being slightly greater than those of PGI2. Both prostaglandins produced dose-related increases in cAMP production over identical concentration ranges (0.01-15 micrograms/ml). Degradation of cAMP, estimated as the difference in tissue levels of cAMP in the presence and absence of maximal amounts of the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX), increased following addition of either prostaglandin with increases paralleling increases in cAMP production. Simultaneous addition of maximal amounts of both prostaglandins resulted in a combined effect on cAMP production which was nonadditive. Both prostaglandins produced dose-related increases in efflux of 45Ca from isolated tubules. Changes in 45Ca efflux were closely related to changes in cAMP levels produced by either prostaglandin. Simultaneous addition of maximal concentrations of PGE1 and PGI2 produced changes in 45Ca efflux which were nonadditive. The results indicate that both prostaglandins increase cAMP production and efflux of calcium in isolated renal cortical tubules and may share a common target cell type in these responses.