Tabrizchi R
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Eur J Pharmacol. 1994 Jul 11;259(3):285-93. doi: 10.1016/0014-2999(94)90655-6.
The effects of an intracellular Ca2+ depletor (ryanodine), a Ca2+ channel antagonist (felodipine), a protein kinase C inhibitor (staurosporine) as well as caffeine, cholera and pertussis toxin have been examined on noradrenaline-induced contractions in aortic rings from rats pretreated i.v. with either saline or phenoxybenzamine for 7 days. Ryanodine (3 and 10 microM) was able to both potentiate and inhibit noradrenaline-evoked contractions in aortic rings from phenoxybenzamine-treated rats. However, ryanodine did not affect the concentration-response curves to noradrenaline in tissues from saline-treated rats. Further, felodipine (1 and 10 nM) and staurosporine (10 nM) inhibited noradrenaline-induced contractions in aortic rings from phenoxybenzamine- but not saline-treated rats. Pertussis toxin (100 ng/ml) also inhibited contractions produced by noradrenaline in rings from phenoxybenzamine- but not saline-treated rats. In contrast to these observations, both caffeine (1 mM) and cholera toxin (3 micrograms/ml) inhibited noradrenaline-evoked contractions in aortic rings from phenoxybenzamine- and saline-treated rats. The results suggest that chronic receptor blockade by phenoxybenzamine leads to alteration in alpha-adrenoceptor-mediated signal transduction in the aorta. The changes include alteration in Ca2+ handling at the plasmalemmal and intracellular levels, as well as an altered action of pertussis toxin-sensitive G-protein, but not of cholera toxin-sensitive G-protein.
已研究了细胞内Ca2+耗竭剂（ryanodine）、Ca2+通道拮抗剂（非洛地平）、蛋白激酶C抑制剂（星形孢菌素）以及咖啡因、霍乱毒素和百日咳毒素对静脉注射生理盐水或苯氧苄胺预处理7天的大鼠主动脉环中去甲肾上腺素诱导的收缩的影响。Ryanodine（3和10 microM）能够增强和抑制苯氧苄胺处理大鼠主动脉环中去甲肾上腺素诱发的收缩。然而，ryanodine不影响生理盐水处理大鼠组织中去甲肾上腺素的浓度-反应曲线。此外，非洛地平（1和10 nM）和星形孢菌素（10 nM）抑制苯氧苄胺处理而非生理盐水处理大鼠主动脉环中去甲肾上腺素诱导的收缩。百日咳毒素（100 ng/ml）也抑制苯氧苄胺处理而非生理盐水处理大鼠主动脉环中去甲肾上腺素产生的收缩。与这些观察结果相反，咖啡因（1 mM）和霍乱毒素（3微克/ml）抑制苯氧苄胺处理和生理盐水处理大鼠主动脉环中去甲肾上腺素诱发的收缩。结果表明，苯氧苄胺的慢性受体阻断导致主动脉中α-肾上腺素能受体介导的信号转导改变。这些变化包括质膜和细胞内水平Ca2+处理的改变，以及百日咳毒素敏感G蛋白而非霍乱毒素敏感G蛋白作用的改变。
