Prostaglandin E2 enhances type 2-bradykinin receptor expression in human glomerular podocytes

Biochim Biophys Acta. 1997 Sep 11;1358(2):142-52. doi: 10.1016/s0167-4889(97)00069-4.

Abstract

We examined the effect of prostaglandin E2 (PGE2) on bradykinin (BK) binding, BK-dependent intracellular calcium and inositol phosphate (i.p.) concentrations and BK mRNA in human glomerular visceral epithelial cells (hGVEC). PGE2 (10 nM) produced a concentration-dependent increase in [3H]-BK specific binding after a lag time of 24 h with a threshold at 0.1 nM. This increase appeared to be mediated exclusively by an increase in BK receptor (BKR)-2 expression. Scatchard analysis of [3H]-BK saturation binding showed that PGE2 produced an increase in the receptor site density without a change in the apparent dissociation constant. PGE2 also markedly stimulated cAMP production. This effect was thought to mediate the increase in expression of BKR-2 as 8-bromo cAMP and various cAMP-stimulating agents acted similarly. PGE2 did not change the BK-dependent intracellular IP3 and cytosolic calcium increases. The overexpression of BKR-2 in the presence of PGE2 was associated with an increase in mRNA as shown by the nuclease protection assay without any change in mRNA half-life. Cycloheximide, an inhibitor of protein synthesis, enhanced BKR-2 mRNA expression. In conclusion, treatment with PGE2 stimulates the synthesis of BKR-2 in hGVEC, possibly by interfering with an inhibitory protein involved in BKR-2 transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Transformed
  • Dinoprostone / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression Regulation / drug effects*
  • Humans
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radioligand Assay
  • Receptors, Bradykinin / genetics*
  • Tritium

Substances

  • RNA, Messenger
  • Receptors, Bradykinin
  • Tritium
  • Dinoprostone