Lipid mediators on the extracellular Ca^<2+>-sensing in parathyroid cells

甲状旁腺细胞通过钙受体（CaR）直接监测细胞外Ca^<2+>浓度。在分离的蛙甲状旁腺细胞中，细胞外高浓度的Ca^<2+>诱导氯离子电导的大幅增加。在本研究中，我们研究了细胞外Ca^<2+>如何增加甲状旁腺氯电导，同时记录全细胞电流。甲状旁腺细胞显示出对TTX敏感的Na^+电流，以响应从-84 mV的保持电位开始的去极化电压阶跃。细胞外Win 55，212-2极大地抑制了电压门控Na+电流，这表明大麻素可以修饰该活性。细胞外高浓度Ca^<2+>诱导-50 mV内向电流增加，并呈剂量依赖性。当<50>细胞外应用U 73122（PLC抑制剂）、tetrahydrolipstatin（DAG脂肪酶抑制剂）或MAFP（MAG脂肪酶抑制剂）时，细胞外Ca^2+诱导电流的幅度显著降低。内透析2-花生四烯酸甘油（2-AG）可诱导Gd^&lt;3+&gt;敏感性内向电流，但内透析2-AG醚不能诱导任何反应。花生四烯酸内透析也可诱导Gd^&lt;3+&gt;敏感性内向电流.结果表明花生四烯酸代谢产物参与了蛙甲状旁腺细胞的细胞外Ca^2+敏感性。

Parathyroid cells directly monitor extracellular Ca^<2+> concentration using Ca receptors(CaR). In isolated frog parathyroid cells, high extracellular Ca^<2+> concentration induces a large increase in chloride conductance. In the present study, we investigated how extracellular Ca^<2+> increases parathyroid chloride conductance while recording the whole cell current. The parathyroid cells displayed a TTX-sensitive Na^+ current in response to the depolarizing voltage steps from a holding potential of -84 mV. Extracellular Win55,212-2 greatly inhibited the voltage-gated Na+ current, suggesting that the activity can be modified by the cannabinoids. High extracellular Ca^<2+> induced an increase of the inward current at -50 mV in a dose-dependent manner. The apparent EC_<50>for Ca^<2+>was about 6 mM. When either U73122(an inhibitor of PLC), tetrahydrolipstatin(an inhibitor of DAG lipase), or methyl arachidonyl fluorophosphonate(MAFP, an inhibitor of MAG lipase)was applied extracellularly, the magnitude of extracellular Ca^<2+>-induced current decreased significantly. Internal dialysis of 2-arachidonyl glycerol(2-AG)induced a Gd^<3+>-sensitive inward current, but internal 2-AG ether did not elicit any response. Internal dialysis of arachidonic acid also induced Gd^<3+>-sensitive inward current. The results suggest that the arachidonic acid metabolite is involved in the extracellular Ca^<2+>-sensing of frog parathyroid cells.