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

Maria E. Marin Castaño, Joost P. Schanstra, Christophe Hirtz, João B. Pesquero, Christiane Pecher, Jean Pierre Girolami, Jean Loup Bascands

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26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)F532-F540
JournalAmerican Journal of Physiology - Renal Physiology
Volume274
Issue number3 43-3
StatePublished - Mar 1 1998

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Keywords

  • Adenosine 3',5'-cyclic monophosphate
  • B kinin receptor messenger ribonucleic acid
  • Bradykinin
  • Free cytosolic calcium
  • Mesangial cell
  • Prostaglandin E

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Marin Castaño, M. E., Schanstra, J. P., Hirtz, C., Pesquero, J. B., Pecher, C., Girolami, J. P., & Bascands, J. L. (1998). B2 kinin receptor upregulation by cAMP is associated with BK-induced PGE2 production in rat mesangial cells. American Journal of Physiology - Renal Physiology, 274(3 43-3), F532-F540.