Journal
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
Volume 291, Issue 4, Pages F891-F895Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajprenal.00512.2005
Keywords
cyclooxygenase-2
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Funding
- Intramural NIH HHS Funding Source: Medline
- NHLBI NIH HHS [R01-HL-079453] Funding Source: Medline
- NIDDK NIH HHS [K01-DK-064981, R01-DK-066592] Funding Source: Medline
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Collecting ducts are a major site of renal production and action of both prostaglandins and nitric oxide. Experiments were undertaken to examine whether nitric oxide regulates cyclooxygenase (COX)-2 expression and PGE(2) release in cultured collecting duct cells. In mIMCD-K2 cells, sodium nitroprusside (SNP) in the 50-to 800-mu M range induced a marked dose-and time-dependent increase in COX-2 protein levels, determined by immunoblotting, and the induction was detectable at 4 h. This was preceded by induction of COX-2 mRNA as determined by real-time-RT-PCR. The COX-2 induction was accompanied by a significant rise in PGE(2) release as determined by enzyme immunoassay. S-nitroso-N-acetylpenicillamine (SNAP) had a similar stimulatory effect on COX-2 expression and PGE(2) release. 8-bromo-cGMP (200 mu M) had no effect on COX-2 expression. The SNP-stimulated COX-2 expression was not affected by the guanylyl cyclase inhibitor methylene blue or the protein kinase G inhibitor KT-5823 (2.0 mu M). In contrast, the SNP-stimulated COX-2 expression was significantly reduced by either the Erk1/ 2 inhibitor PD-98059 or the P38 inhibitor SB-203580 and was abolished by combination of the two kinase inhibitors. The stimulation was also significantly blocked by the SOD mimetic tempol. Thus we conclude that NO stimulates COX-2 expression in collecting duct cells through mechanisms involving MAP kinase and superoxide, but not cGMP.
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