B2 kinin receptor upregulation by cAMP is associated with BK-induced PGE2 production in rat mesangial cells

In the rat mesangial cell (MC), activation of the bradykinin B(2) receptor (B(2)R) by bradykinin (BK) is associated with both phospholipase C (PLC) and A(2) (PLA(2)) 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 B(2) mRNA expression, on the density of B(2) receptor binding sites, on the BK-induced increase in both the free cytosolic Ca(2+) concentration ([Ca(2+)](i)), and in the prostaglandin E(2) (PGE(2)) production. Forskolin, PGE(2), and cAMP analog, 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP), were used to increase [cAMP](i). Twenty-four-hour treatment with forskolin, PGE(2), and 8-BrcAMP resulted in significant increases in B(2) receptor binding sites, which were inhibited by cycloheximide. The maximum B(2) receptor mRNA expression (160% above control) was observed in cells treated during 24 h with forskolin and was prevented by actinomycin D. In contrast, the D-myo-inositol 1,4,5-trisphosphate (IP(3)) formation and the BK-induced increase in [Ca(2+)](i), reflecting activation of PLC, were not affected by increased levels of [cAMP](i). However, the BK-induced PGE(2) release, reflecting PLA(2) activity, was significantly enhanced. These data bring new information regarding the dual signaling pathways of B(2) receptors that can be differentially regulated by cAMP.