Low concentrations of prostaglandin E2 inhibit the prostacyclin-induced elevation of cyclic adenosine 3',5'-monophosphate in elicited populations of rat peritoneal macrophages.

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. PGE2, within the range of 1.4 X 10(-9) to 1.2 X 10(-8)M, caused a concentration-dependent inhibition of the rise in cyclic AMP induced by 2.8 X 10(-6) M PGI2 or DDH-carbo-PGI2. With higher concentrations of PGE2 the inhibition was either non-existent or masked by the effect of PGE2 per se on cyclic AMP levels. 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.