Abebe W, Harris K H, MacLeod K M
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
J Cardiovasc Pharmacol. 1990 Aug;16(2):239-48. doi: 10.1097/00005344-199008000-00010.
The purpose of this study was to determine the receptor subtype mediating enhanced contractile responses of aortae and mesenteric arteries from diabetic rats to the alpha-adrenoceptor agonists, norepinephrine, clonidine, and methoxamine and to establish whether the enhanced responses are associated with increased release of intracellular Ca2+ or are dependent on the presence of extracellular Ca2+. The pA2 values calculated for the alpha 1-selective antagonist prazosin were similar in arteries from control and diabetic rats and were 2.5-3 log units greater than pA2 values calculated for the alpha 2-selective antagonist yohimbine. Contractile responses of aortae incubated in Ca2(+)-free Krebs' solution containing 1 mM EGTA to maximal but not to ED50 concentrations of the alpha-adrenoceptor agonists were significantly greater in preparations from diabetic than from control rats. Following readdition of Ca2+, contractile responses of diabetic aortae to all concentrations of the agonists tested were significantly greater than control. Similar results were obtained in mesenteric arteries, except that no clonidine response could be detected in preparations from either diabetic or control rats in the absence of extracellular Ca2+. These data indicate that enhanced responses of arteries from diabetic rats to alpha-adrenoceptor agonists are mediated by alpha 1 adrenoceptors, and are largely dependent on the presence of extracellular Ca2+. However, increased release of intracellular Ca2+ appears to contribute to enhanced responses to high concentrations of these agonists.
本研究的目的是确定介导糖尿病大鼠主动脉和肠系膜动脉对α-肾上腺素能激动剂去甲肾上腺素、可乐定和甲氧明收缩反应增强的受体亚型，并确定这种增强的反应是否与细胞内Ca2+释放增加有关，或者是否依赖于细胞外Ca2+的存在。为α1选择性拮抗剂哌唑嗪计算的pA2值在对照大鼠和糖尿病大鼠的动脉中相似，并且比为α2选择性拮抗剂育亨宾计算的pA2值大2.5 - 3个对数单位。在含有1 mM乙二醇双四乙酸（EGTA）的无Ca2+ Krebs溶液中孵育的主动脉，对α-肾上腺素能激动剂的最大浓度而非半数有效浓度（ED50）的收缩反应，在糖尿病大鼠的标本中显著大于对照大鼠。重新添加Ca2+后，糖尿病主动脉对所有测试浓度激动剂的收缩反应均显著大于对照。在肠系膜动脉中也获得了类似的结果，只是在没有细胞外Ca2+的情况下，无论是糖尿病大鼠还是对照大鼠的标本中都检测不到可乐定反应。这些数据表明，糖尿病大鼠动脉对α-肾上腺素能激动剂的增强反应是由α1肾上腺素能受体介导的，并且在很大程度上依赖于细胞外Ca2+的存在。然而，细胞内Ca2+释放增加似乎有助于对这些激动剂高浓度的增强反应。
