信号转导通路对毒胡萝卜素作用于大鼠肥大细胞的影响。细胞信号传导与胞质pH之间的相互作用。

Effect of signal transduction pathways on the action of thapsigargin on rat mast cells. Crosstalks between cellular signalling and cytosolic pH.

作者信息

Alfonso A, Botana M A, Vieytes M R, Louzao M C, Botana L M

机构信息

Departamento de Farmacología, Facultad de Veterinaria, Lugo, Spain.

出版信息

Biochem Pharmacol. 1994 May 18;47(10):1813-20. doi: 10.1016/0006-2952(94)90310-7.

DOI:10.1016/0006-2952(94)90310-7

PMID:7515622

Abstract

Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells are pretreated with thapsigargin before the addition of external calcium. Okadaic acid does not modify the response of mast cells to thapsigargin, while sodium fluoride or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) increases several fold the sensitivity of cells to thapsigargin. On the other hand, pertussis and cholera toxins inhibit the response to thapsigargin. Thapsigargin increases the activity of the Na(+)-H+ exchanger, this effect being blocked by fluoride and not modified by TPA. The metals cadmium and lanthanum completely block the effect of TPA or thapsigargin on the Na(+)-H+ exchanger. The influx of 45Ca in rat mast cells is not modified by thapsigargin, but if cells are treated with thapsigargin before the addition of calcium, the influx is markedly increased in the first 2 min before returning to normal. Our results indicate that exocytosis is modulated by crosstalks between intracellular calcium, cytosolic pH and external calcium.

摘要

毒胡萝卜素可诱导大鼠肥大细胞释放组胺，若在添加细胞外钙之前先用毒胡萝卜素预处理细胞，则这种效应会增强。冈田酸不会改变肥大细胞对毒胡萝卜素的反应，而氟化钠或佛波酯12 - O - 十四酰佛波醇 - 13 - 乙酸酯（TPA）会使细胞对毒胡萝卜素的敏感性提高数倍。另一方面，百日咳毒素和霍乱毒素会抑制对毒胡萝卜素的反应。毒胡萝卜素会增加Na(+)-H+交换体的活性，这种效应会被氟化物阻断，且不受TPA影响。镉和镧这两种金属会完全阻断TPA或毒胡萝卜素对Na(+)-H+交换体的作用。毒胡萝卜素不会改变大鼠肥大细胞中45Ca的内流，但如果在添加钙之前用毒胡萝卜素处理细胞，则在恢复正常之前的最初2分钟内，内流会显著增加。我们的结果表明，胞吐作用受细胞内钙、胞质pH值和细胞外钙之间的相互作用调节。