Nakashima M, Vanhoutte P M
Center for Experimental Therapeutics, Baylor College of Medicine, Houston, Texas.
J Pharmacol Exp Ther. 1995 Jan;272(1):379-84.
Experiments were designed to determine how isoproterenol affects the cell membrane potential of smooth muscle cells of the canine saphenous vein. Measurements of membrane potential were performed using glass microelectrodes. Isoproterenol (10(-9) to 10(-6) M) caused sustained, concentration-dependent membrane hyperpolarizations in tissues with and without endothelium. ICI 118,551 (a selective beta 2-adrenoceptor antagonist), but not atenolol (a selective beta 1-adrenoceptor antagonist), abolished the hyperpolarization to isoproterenol. Forskolin, an activator of adenylate cyclase, produced sustained hyperpolarizations, which were not mimicked by 1,9-dideoxyforskolin. Incubation with either ouabain or extracellular K(+)-free solution did not inhibit the electrical response to isoproterenol. Glibenclamide (a selective ATP-sensitive K+ channel antagonist) attenuated the hyperpolarizations induced by either isoproterenol or forskolin, whereas charybdotoxin (an inhibitor of large conductance Ca(++)-activated K+ channels) did not. These findings suggest that isoproterenol opens ATP-sensitive K+ channels indirectly through activation of adenylate cyclase in the smooth muscle of the canine saphenous vein. The adrenergic receptor involved belongs to the beta 2-adrenoceptor subtype.
实验旨在确定异丙肾上腺素如何影响犬隐静脉平滑肌细胞的细胞膜电位。使用玻璃微电极进行膜电位测量。异丙肾上腺素（10⁻⁹至10⁻⁶M）在有内皮和无内皮的组织中均引起持续的、浓度依赖性的膜超极化。ICI 118,551（一种选择性β₂肾上腺素能受体拮抗剂）而非阿替洛尔（一种选择性β₁肾上腺素能受体拮抗剂）可消除对异丙肾上腺素的超极化作用。腺苷酸环化酶激活剂福斯可林产生持续的超极化，1,9 - 二脱氧福斯可林不能模拟该作用。用哇巴因或细胞外无钾溶液孵育并不抑制对异丙肾上腺素的电反应。格列本脲（一种选择性ATP敏感性钾通道拮抗剂）减弱了由异丙肾上腺素或福斯可林诱导的超极化，而大电导钙激活钾通道抑制剂蝎毒素则无此作用。这些发现表明，异丙肾上腺素通过激活犬隐静脉平滑肌中的腺苷酸环化酶间接打开ATP敏感性钾通道。所涉及的肾上腺素能受体属于β₂肾上腺素能受体亚型。
