Ionomycin restores taurine transporter activity in cyclosporin-A treated macrophages.

Abstract

Taurine is accumulated at high concentrations in various tissues. The taurine transporter (TAUT) is responsible for the transportation of taurine in the cell. The transporter is affected by various stimuli to maintain cell volume. Macrophage cell volume varies in its activated states. In our experiment, it was found that the murine macrophage cell line, RAW264.7, expressed TAUT protein in its membrane. Its transporting activities could be blocked by beta-amino acid such as beta-alanine, but not by alpha-amino acids in this cell line, when assessed in RAW264.7 cells under the influence of immunosuppressive reagents, the activity of the TAUT was decreased by treatment with rapamycin (RM) or cyclosporin A (CSA). However, when ionomycin (IM) was added to this system, TAUT activity was recovered only in CSA-treated cells, in a concentration-dependent manner, in order to inhibit voltage gated Ca2+ channels, calmidazolium was added to the RAW264.7 cell line. Treatment of the cells with calmidazolium completely blocked TAUT. Furthermore, addition of IM to this system resulted in recovery the activity of TAUT again. When we added phorbol myristyl acetate (PMA) to the cell line, secretion of nitric oxide (NO) was increased 4-fold and the TAUT activity was decreased 5-fold. However, the addition of N-nitro L-arginine methyl ester (L-NAME), an inducible NO synthase (iNOS) inhibitor, to the PMA-treated cells induced recovery of TAUT activity. These results showed that the activity of TAUT was sensitive to both the intracellular concentrations of Ca2+ and NO.