DAG lipase-lipoxygenase pathway in Ca sensing of parathyroid cells

点击翻译按钮获取中文摘要

Elevation of extracellular Ca^<2+> concentration induces intracellular Ca^<2+> signaling in parathyroid cells. We report the electrophysiological property associated with intracellular Ca^<2+> signaling in frog parathyroid cells and show that Ca^<2+>-activated Cl- channels are activated by intracellular Ca^<2+> increase through inositol 1,4,5-trisphophate (IP3)-independent pathway. High extracellular Ca^<2+> induced an outwardly-rectifying conductance in a dose-dependent manner. The conductance was composed of an instantaneous time-independent component and a slowly activating time-dependent component and displayed deactivating inward tail current. Extracellular Ca^<2+>-induced and Ca^<2+> dialysis-induced currents reversed at the equilibrium potential of Cl- and were inhibited by niflumic acid. Extracellular Ca^<2+>-induced currents displayed a moderate dependency on guanosine triphosphate (GTP). All blockers for phospholipase C, DAG lipase, MAG lipase and lipoxygenase inhibited extracellular Ca^<2+>-induced current. IP3 dialysis failed to induce conductance increase, but 2-AG, arachidonic acid and 12(S)-HPETE dialysis increased the conductance identical to extracellular Ca^<2+>-induced conductance. These results indicate high extracellular Ca^<2+> raises intracellular Ca^<2+> concentration through DAG lipase/lipoxygenase pathway, resulting in the activation of Cl^-conductance.