Prostaglandin E2 enhances type 2-bradykinin receptor expression in human glomerular podocytes.
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.
Costenbader
K
K
INSERM 64, Hôpital Tenon, Paris, France.
Ardaillou
N
N
Marchetti
J
J
Placier
S
S
Ardaillou
R
R
D002461:Cell Line, Transformed; D015232:Dinoprostone / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011869:Radioligand Assay; D018002:Receptors, Bradykinin / Q000235:genetics*; D014316:Tritium
D012333:RNA, Messenger; D018002:Receptors, Bradykinin; D014316:Tritium; D015232:Dinoprostone