RAPID CHANGES IN THE ACTIVITIES OF THE ENZYMES OF CYCLIC-AMP METABOLISM AFTER ADDITION OF A23187 TO MACROPHAGES

The ionophore A23187 [calcimycin] stimulated adenylate cyclase activity in intact rat macrophages within 1 min. This action was blocked by pretreatment with indomethacin (25 .mu.ol/l), suggesting prostaglandin (PG) involvement. PGE2 (500 nmol/l) also stimulated adenylate cyclase activity in intact cells, but this was not prevented by indomethacin pretreatment. Colchicine (100 .mu.ol/l) potentiated the increases in macrophage cAMP production seen after addition of PGE2 or A23187. The high affinity form of cAMP phosphodiesterase (PDE) was activated within 1 min of the addition of A23187 to intact macrophages. The increase in macrophage cAMP production after A23187 possibly is a consequence of adenylate cyclase activation and not PDE inhibition. The endogenous production of a PG probably mediates this effect of A23187, emphasizing the importance of arachidonic acid metabolites in the regulation of macrophage functions.