B2 kinin receptor upregulation by cAMP is associated with BK-induced PGE2 production in rat mesangial cells.
Am J Physiol
; 274(3): F532-40, 1998 03.
Article
in En
| MEDLINE
| ID: mdl-9580144
ABSTRACT
In the rat mesangial cell (MC), activation of the bradykinin B2 receptor (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 B2 mRNA expression, on the density of B2 receptor 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 B2 receptor binding sites, which were inhibited by cycloheximide. The maximum B2 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 (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 PGE2 release, reflecting PLA2 activity, was significantly enhanced. These data bring new information regarding the dual signaling pathways of B2 receptors that can be differentially regulated by cAMP.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bradykinin
/
Dinoprostone
/
Receptors, Bradykinin
/
Cyclic AMP
/
Glomerular Mesangium
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol
Year:
1998
Document type:
Article
Affiliation country:
France