In the rat mesangial cell (MC), activation of the bradykinin B2receptor (B2R) by bradykinin (BK) is associated with both phospholipase C (PLC) and A2(PLA2) activities and with inhibition of adenosine 3′,5′-cyclic monophosphate (cAMP) formation leading to cell contraction. Because cAMP plays an important role in the regulation of gene expression in general, we investigated the effect of increasing the intracellular cAMP concentration ([cAMP]i) in mesangial cells on the B2mRNA expression, on the density of B2receptor binding sites, on the BK-induced increase in both the free cytosolic Ca2+concentration ([Ca2+]i), and in the prostaglandin E2(PGE2) production. Forskolin, PGE2, and cAMP analog, 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP), were used to increase [cAMP]i. Twenty-four-hour treatment with forskolin, PGE2, and 8-BrcAMP resulted in significant increases in B2receptor binding sites, which were inhibited by cycloheximide. The maximum B2receptor mRNA expression (160% above control) was observed in cells treated during 24 h with forskolin and was prevented by actinomycin D. In contrast, thed- myo-inositol 1,4,5-trisphosphate (IP3) formation and the BK-induced increase in [Ca2+]i, reflecting activation of PLC, were not affected by increased levels of [cAMP]i. However, the BK-induced PGE2release, reflecting PLA2activity, was significantly enhanced. These data bring new information regarding the dual signaling pathways of B2receptors that can be differentially regulated by cAMP.