Garcha R S, Hughes A D
Department of Clinical Pharmacology, St. Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, England.
J Cardiovasc Pharmacol. 1995 May;25(5):840-6. doi: 10.1097/00005344-199505000-00022.
We examined the effects of ryanodine and thapsigargin on changes in cytoplasmic [Ca2+] (Cai) and muscle tension in rat mesenteric resistance arteries induced by norepinephrine (NE) and caffeine. Both ryanodine and thapsigargin markedly inhibited the increase in Cai and contractile responses to caffeine in physiological saline and to NE and caffeine in calcium-free conditions. In contrast, peak responses to potassium depolarisation and NE in physiological saline appeared little affected, although time taken to achieve 50% of peak response after addition of NE was slowed after ryanodine and thapsigargin treatment. Neither ryanodine nor thapsigargin altered resting tone or Cai or the Ca2+ sensitivity of contraction under depolarized conditions. The NE concentration-response relationship was not significantly altered after ryanodine or thapsigargin. Ryanodine and thapsigargin inhibit the release of intracellular Ca2+ stores by NE and caffeine. Inhibition of release of intracellular Ca2+ by NE has only slight effects on contractile responses of mesenteric resistance arteries when extracellular Ca2+ is present.
我们研究了ryanodine和毒胡萝卜素对去甲肾上腺素（NE）和咖啡因诱导的大鼠肠系膜阻力动脉细胞质[Ca2+]（Cai）变化和肌肉张力的影响。在生理盐水中，ryanodine和毒胡萝卜素均显著抑制Cai的升高以及对咖啡因的收缩反应，在无钙条件下，它们还抑制对NE和咖啡因的收缩反应。相比之下，在生理盐水中，对钾去极化和NE的峰值反应似乎受影响较小，尽管在ryanodine和毒胡萝卜素处理后，加入NE后达到峰值反应50%所需的时间变慢。在去极化条件下，ryanodine和毒胡萝卜素均未改变静息张力、Cai或收缩的Ca2+敏感性。ryanodine或毒胡萝卜素处理后，NE浓度-反应关系未发生显著改变。Ryanodine和毒胡萝卜素抑制NE和咖啡因引起的细胞内Ca2+储存释放。当细胞外Ca2+存在时，NE对细胞内Ca2+释放的抑制对肠系膜阻力动脉的收缩反应仅有轻微影响。
