Mem. Castano et al., B-2 KININ RECEPTOR UP-REGULATION BY CAMP IS ASSOCIATED WITH BK-INDUCED PGE(2) PRODUCTION IN RAT MESANGIAL CELLS, American journal of physiology. Renal, fluid and electrolyte physiology, 43(3), 1998, pp. 532-540
In the rat mesangial cell (MC), activation of the bradykinin B-2 recep
tor (B2R) 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 express
ion in general, we investigated the effect of increasing the intracell
ular 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-i
nduced increase in both the free cytosolic Ca2+ concentration ([Ca2+](
i)), and in the prostaglandin E-2 (PGE(2)) production. Forskolin, PGE(
2), and cAMP analog, 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br
cAMP), were used to increase [cAMP](i). Twenty-four-hour treatment wit
h forskolin, PGE(2), and 8-BrcAMP resulted in significant increases in
B-2 receptor binding sites, which were inhibited by cycloheximide. Th
e maximum B-2 receptor mRNA expression (160% above control) was observ
ed in cells treated during 24 h with forskolin and was prevented by ac
tinomycin D. In contrast, the D-myo-inositol 1,4,5-trisphosphate (IP3)
formation and the BK-induced increase in [Ca2+](i), reflecting activa
tion of PLC, were not affected by increased levels of [cAMP](i). Howev
er, the BK-induced PGE(2) release, reflecting PLA(2) activity, was sig
nificantly enhanced. These data bring new information regarding the du
al signaling pathways of B-2 receptors that can be differentially regu
lated by cAMP.