Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry.
Maitotoxin effects are blocked by SK&F 96365, an inhibitor of receptor-mediated calcium entry.
复制标题
麦芽毒素作用被 SK 阻断
作者：
D. Soergel;T. Yasumoto;J. Daly;F. Gusovsky
甲藻毒素maitotoxin（MTX）可引起C6胶质瘤细胞内[Ca ~（2+）]i持续升高。这种反应被SK&F 96365抑制，SK & F 96365是一种受体介导的钙离子进入的阻断剂。在C6细胞中，内皮素-1引起[Ca 2 +]i的快速但短暂的增加，随后是较小的持续增加。SK&F 96365抑制[Ca ~（2+）]i的持续升高。在C6胶质瘤细胞和RIN胰岛素瘤细胞中，MTX引起了显著的45 Ca ~（2+）内流。SK&F 96365在30 μ M时抑制MTX诱导的45 Ca 2+内流达95%。L-型钙通道阻滞剂硝苯地平，即使在10 μ M，抑制MTX诱导的钙摄取只有20%，在RIN细胞和C6细胞只有10%。MTX引起C6和RIN细胞中钙依赖性磷酸肌醇的分解。在两种细胞系中，MTX诱导的磷酸肌醇分解被30 μ M的SK&F 96365抑制90%。内皮素-1和氨甲酰胆碱分别引起C6细胞和RIN细胞的磷酸肌醇分解。刺激不受SK&F 96365存在的影响，高达100 μ M。在RIN胰岛素瘤细胞中，MTX引起胰岛素的钙依赖性释放。SK&F 96365在30 μ M时抑制MTX诱导的胰岛素释放75%，而硝苯地平即使在30 μ M时也仅抑制10%的释放。SK&F 96365对MTX诱导的反应的阻断表明MTX通过直接与钙进入系统相互作用来增加细胞内钙，所述钙进入系统在其对SK&F 96365的敏感性方面类似于由引起磷酸肌醇分解的受体激活的钙进入系统。SK&F 96365也可阻断MTX对磷脂酶C的激活和激素释放，因此，这可能是继发于钙离子进入系统的激活。
The dinoflagellate toxin maitotoxin (MTX) elicited a sustained increase of [Ca2+]i in C6 glioma cells. This response was inhibited by SK&F 96365, a blocker of receptor-mediated calcium entry. In C6 cells, endothelin-1 elicited a rapid but transient increase in [Ca2+]i, followed by a smaller sustained increase. SK&F 96365 inhibited the sustained increase in [Ca2+]i. In both C6 glioma cells and RIN insulinoma cells, MTX elicited a marked influx of 45Ca2+. SK&F 96365 inhibited MTX-induced 45Ca2+ influx by 95% at 30 microM. The L-type calcium channel blocker nifedipine, even at 10 microM, inhibited MTX-induced calcium uptake by only 20% in RIN cells and by only 10% in C6 cells. MTX elicited calcium-dependent phosphoinositide breakdown in both C6 and RIN cells. In both cell lines, the MTX-induced phosphoinositide breakdown was inhibited by 90% by SK&F 96365 at 30 microM. Endothelin-1 and carbamylcholine elicited phosphoinositide breakdown in C6 cells and RIN cells, respectively. The stimulations were unaffected by the presence of SK&F 96365 up to 100 microM. In RIN insulinoma cells, MTX elicited calcium-dependent release of insulin. SK&F 96365 at 30 microM inhibited MTX-induced insulin release by 75%, whereas nifedipine, even at 30 microM, inhibited release by only 10%. The blockade of MTX-induced responses by SK&F 96365 indicates that MTX increases intracellular calcium by interacting directly with a calcium-entry system that is similar, in its sensitivity to SK&F 96365, to the calcium-entry system activated by receptors that elicit phosphoinositide breakdown. Activation of phospholipase C and hormone release by MTX also are blocked by SK&F 96365 and, thus, may be secondary to the activation of such a calcium-entry system.