Mikkelsen E O, Thastrup O, Christensen S B
Institute of Pharmacology, University of Aarhus, Denmark.
Pharmacol Toxicol. 1988 Jan;62(1):7-11. doi: 10.1111/j.1600-0773.1988.tb01835.x.
The effect of thapsigargin (Tg) was studied in rat thoracic aorta. Tg (10(-8)-10(-5) M) had a dual effect on rat aorta. Thus, Tg induced a concentration dependent increase in basal tone in normal physiological salt solution (PSS), while Tg in potassium (K+) precontracted aortic rings caused a concentration related relaxation and shifted the K+-concentration response curve to the right and depressed the maximal response to K+. Removal of vascular endothelium abolished the relaxant response to Tg and increased the sensitivity of the preparations to the contractile effect of Tg. The contractile response to Tg was resistent to wash-out in drug-free PSS and was not affected by phentolamine, indomethacin or mepyramine but partly reduced by the calcium-antagonist nitrendipine and eliminated by wash-out in calcium-free PSS. Atropine eliminated the endothelium dependent relaxant effect of carbachol, but had no effect on the Tg or on the calcium ionophore A 23187 evoked relaxation. Ultraviolet radiation decreased the relaxant effect of Tg and A 23187 without affecting the carbachol induced relaxations. The results showed that vascular endothelium depressed the contractile effect of Tg and that Tg like A 23187 had an endothelium dependent relaxant effect on rat aorta different from that of carbachol. The results indicate that Tg in vascular smooth muscle acts by stimulating the transmembranal influx of extracellular calcium.
研究了毒胡萝卜素（Tg）对大鼠胸主动脉的作用。Tg（10⁻⁸ - 10⁻⁵ M）对大鼠主动脉有双重作用。因此，在正常生理盐溶液（PSS）中，Tg诱导基础张力呈浓度依赖性增加，而在钾（K⁺）预收缩的主动脉环中，Tg引起浓度相关的舒张，并使K⁺浓度反应曲线右移，降低对K⁺的最大反应。去除血管内皮消除了对Tg的舒张反应，并增加了制剂对Tg收缩作用的敏感性。对Tg的收缩反应在无药的PSS中对冲洗有抵抗性，且不受酚妥拉明、吲哚美辛或美吡拉敏影响，但部分被钙拮抗剂尼群地平降低，并在无钙PSS中冲洗后消除。阿托品消除了卡巴胆碱的内皮依赖性舒张作用，但对Tg或钙离子载体A 23187引起的舒张无影响。紫外线辐射降低了Tg和A 23187的舒张作用，而不影响卡巴胆碱诱导的舒张。结果表明，血管内皮抑制了Tg的收缩作用，且Tg与A 23187一样，对大鼠主动脉有不同于卡巴胆碱的内皮依赖性舒张作用。结果表明，血管平滑肌中的Tg通过刺激细胞外钙的跨膜内流起作用。
