LOW CONCENTRATIONS OF PROSTAGLANDIN E2 INHIBIT THE PROSTACYCLIN-INDUCED ELEVATION OF CYCLIC ADENOSINE 3′,5′-MONOPHOSPHATE IN ELICITED POPULATIONS OF RAT PERITONEAL MACROPHAGES

Abstract

1 Elevation of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in elicited populations of rat peritoneal macrophages was used as a parameter to examine the influence of prostaglandin E₂ (PGE₂) on the effects of prostacyclin (PGI₂) and (±)-5E-13,14-didehydro-carbo-prostacyclin (DDH-carbo-PGI₂) in vitro. 2 PGE₂, within the range of 1.4 × 10⁻⁹ to 1.2 × 10⁻⁸ m, caused a concentration-dependent inhibition of the rise in cyclic AMP induced by 2.8 × 10⁻⁶ m PGI₂ or DDH-carbo-PGI₂. 3 With higher concentrations of PGE₂ the inhibition was either non-existent or masked by the effect of PGE₂ per se on cyclic AMP levels. 4 The present findings suggest that the earlier observed low responsiveness of granuloma macrophages to PGI₂, in terms of rise in cyclic AMP, is possibly due to permanent exposure of these cells to environmental endogenous PGE₂.