前肾小球平滑肌细胞中内皮素介导的钙信号(英文)

Endothelin-mediated calcium signaling in preglomerular smooth muscle cells

Abstract This study was performed to test the hypothesisthat endothelin peptides differentially influence intracellularcalcium concentration([Ca^(2+)]i) in preglomerular microvascu-lar smooth muscle cells (MVSMC),in part through activationof endothelin (ET) A receptors.Experiments were performedin vitro with the use of single MVSMC freshly isolated fromrat preglomerular microvessels.The effect of ET-1,ET-2,and ET-3 on[Ca^(2+)]i was measured with the use of the calci-um-sensitive dye, fura 2, and standard fluorescence mi-croscopy techniques. Baseline [Ca^(2+)]i averaged (84±3)nmol/L (n=141 cells from 23 dispersions). ET-1 concentra-tions of 1,10,and 100 nmol/L evoked peak increases in[Ca^(2+)]i of(48±16),(930±125),and (810±130)nmol/L,respectively.The time course of the [Ca^(2+)]i response wasbiphasic,beginning with a rapid initial increase followed by asustained plateau phase or a period during which [Ca^(2+)]i os-cillated sharply.Similar responses were observed after ET-2administration.In contrast。

Abstract This study was performed to test the hypothesis that endothelin peptides differentially influence intracellular calcium concentration([Ca2+]i) in preglomerular microvascu-lar smooth muscle cells(MVSMC) ,in part through activation of endothelin(ET) A receptors. Experiments were performed in vitro with the use of single MVSMC freshly isolated from rat preglomerular microvessels. The effect of ET-l,ET-2, and ET-3 on [Ca2+]i was measured with the use of the calcium-sensitive dye, fura 2, and standard fluorescence microscopy techniques. Baseline [Ca2+]i averaged (84±3) nmol/L(n = 141 cells from 23 dispersions). ET-1 concentrations of 1,10, and 100 nmol/L evoked peak increases in [Ca2+]i of (48±16),(930±125),and (810±130) nmol/L, respectively. The time course of the [Ca2+]i response was biphasic,beginning with a rapid initial increase followed by a sustained plateau phase or a period during which [Ca2+]i oscillated sharply. Similar responses were observed after ET-2 administration. In contrast, ET-3 stimulated monophasic in-creases in [Ca2+]i of only (14±5),(33±16),and (44±19) nmol/L at peptide concentrations of 1,10,and 100 nmol/L, respectively. These responses are significantly smaller than responses to ET-1 or ET-2,respectively. The relative contributions of calcium mobilization and calcium influx in the response to ET-1 were also evaluated. Removal of calcium from the bathing medium did not significantly alter the peak response to 10 nmol/L ET-1 but abolished the late phase elevation of [Ca2+]i. These data demonstrate that endothelin pep-tides increase [Ca2+]i in preglomerular MVSMC. The concentration-response profiles are consistent with the response involving activation of ETA receptors. Furthermore,these results suggest that ET-1 increases [Ca2+]i by stimulating both the release of intracellular calcium and the influx of calcium from the extracellular medium.