抄録
The kidney macula densa (MD) control the tubuloglomerular feedback (TGF) system for regulation of the total body fluid volume. The MD cells express cyclooxygenase-2 (COX-2) and COX-2-derived prostaglandins stimulate the renin release from the granular cells of afferent artelioles, especially during volume depletion. However, the subcellular signaling mechanism of COX-2 gene expression remains unclear. For this purpose, newly established mouse macula densa cells (NE-MD) were used to directly determine whether COX-2 gene expression was regulated by either low [NaCl] concentration or intracellular cAMP/Ca2+. In the present study, COX-2 gene expression was evaluated by real-time quantitative PCR. Real-time PCR showed a significant increase in COX-2 gene expression in the samples with low [Cl−] solution and culture media plus furosemide, an inhibitor of Na+-K+-2Cl− cotransporter, compared to controls. However, no increase was observed in the samples with a low [Na+] solution. Low Cl−-induced increase in COX-2 expression was completely reversed in the presence of either BAPTA-AM, a membrane-permeable Ca2+ chelator, EIPA, an inhibitor of Na+/H+ exchanger, or H-89, an inhibitor of protein kinase A. Finally, COX-2 gene expression was significantly increased in the presence of forskolin (normal solution), whereas it was reversed by H-89. In conclusion, low [Cl−]-induced COX-2 gene expression may be regulated by intracellular cAMP, pH, Ca2+, and [NaCl]. [J Physiol Sci. 2007;57 Suppl:S218]
