Low chloride stimulation of prostaglandin E2 release and cyclooxygenase-2 expression in a mouse macula densa cell line

Tianxin Yang, John M. Park, Lois Arend, Yuning Huang, Rezan Topaloglu, Anita Pasumarthy, Helle Praetorius, Kenneth Spring, Josephine P. Briggs, Jurgen Schnermann

Research output: Contribution to journalArticlepeer-review

Abstract

Reducing luminal NaCl concentration in the macula densa region of the nephron stimulates renin secretion, and this response is blocked by a specific inhibitor of cyclooxygenase-2 (COX-2) (Traynor, T. R., Smart, A., Briggs, J. P., and Schnermann, J. (1999) Am. J. Physiol. Renal Physiol. 277, F706-710). To study whether low NaCl activates COX-2 activity or expression we clonally derived a macula densa cell line (MMDD1 cells) from SV-40 transgenic mice using fluorescence-activated cell sorting of renal tubular cells labeled with segment-specific fluorescent lectins. MMDD1 cells express COX-2, bNOS, NKCC2, and ROMK, but not Tamm-Horsfall protein, and showed rapid 86Rb+ uptake that was inhibited by a reduction in NaCl concentration and by bumetanide or furosemide. Isosmotic exposure of MMDD1 cells to low NaCl (80 mM) caused a prompt and time-dependent stimulation of prostaglandin E2 (PGE2) release that was prevented by the COX-2 specific inhibitor NS-398 (10 μM). Reducing NaCl to 60 and 6 mM for 16 h increased COX-2 expression in a chloride-dependent fashion. Low NaCl phosphorylated p38 kinase within 30 rain and ERK1/2 kinases within 15 min without changing total MAP kinase levels. Low NaCl-stimulated PGE2 release and COX-2 expression was inhibited by SB 203580 and PD 98059 (10 μM), inhibitors of p38 and ERK kinase pathways. We conclude that low chloride stimulates PGE2 release and COX-2 expression in MMDD1 cells through activation of MAP kinases.

Original languageEnglish (US)
Pages (from-to)37922-37929
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number48
DOIs
StatePublished - Dec 1 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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