https://www.selleckchem.com/products/opb-171775.html Ca2+ oscillations that depend on inositol-1,4,5-trisphosphate (IP3) have been ascribed to biphasic Ca2+ regulation of the IP3 receptor (IP3R) or feedback mechanisms controlling IP3 levels in different cell types. IP3 uncaging in hepatocytes elicits Ca2+ transients that are often localized at the subcellular level and increase in magnitude with stimulus strength. However, this does not reproduce the broad baseline-separated global Ca2+ oscillations elicited by vasopressin. Addition of hormone to cells activated by IP3 uncaging initiates a qualitative transition from high-frequency spatially disorganized Ca2+ transients, to low-frequency, oscillatory Ca2+ waves that propagate throughout the cell. A mathematical model with dual coupled oscillators that integrates Ca2+-induced Ca2+ release at the IP3R and mutual feedback mechanisms of cross-coupling between Ca2+ and IP3 reproduces this behavior. Thus, multiple Ca2+ oscillation modes can coexist in the same cell, and hormonal stimulation can switch from the simpler to the more complex to yield robust signaling. Cisplatin (CDDP) has been a highly successful anticancer drug in cancer therapy; however, its further application suffers severe nephrotoxicity. Herein, we identify bismuth tetraphenylporphyrinate [Bi(TPP)] as a potent protective agent against CDDP-induced nephrotoxicity. Bi(TPP) attenuates CDDP-induced acute kidney injury and prevents the death of mice exposed to a lethal dose of CDDP. The protective potency of bismuth porphyrin complexes could be optimized by varying lipophilic TPP ligands with ideal ClogP values of 8-14. Unexpectedly, Bi(TPP) exhibited a protective role via metallothionein-independent pathways, i.e., maintenance of redox homeostasis and energy supplement, elimination of accumulated platinum in the kidney, and inactivation of caspases cascade in apoptotic pathway. Significantly, Bi(TPP) does not compromise the antitumor activity of CDDP in the