Nagykáldi Z, Kem D, Lazzara R, Szabó B
Department of Internal Medicine, University of Oklahoma HSC, Oklahoma City, USA.
Acta Pharm Hung. 1999 Nov;69(5):247-57.
To establish the functional coupling of beta adrenoceptor (beta AR) subtypes of beta 1AR and beta 2AR to L-type calcium current (ICaL), we investigated the non-selective agonist isoproterenol (ISO), and the relatively selective beta 2AR agonists zinterol (ZIN) and salbutamol (SAL) on ICaL in isolated canine ventricular myocytes in the presence and absence of CGP 20712A (CGP) and atenolol (AT), selective beta 1AR antagonists, and ICI 118,551 (ICI) a selective beta 2AR antagonist. Peak ICaL was determined using "patch type" microelectrodes and whole cell voltage clamp. ISO (0.5 microM) increased ICaL maximally 3.5 +/- 0.67 fold. ZIN (10.0 microM) and SAL (10.0 microM) increased ICaL maximally 1.5 +/- 0.2 (n = 5) fold and 1.4 +/- 0.1 (n = 5) fold, respectively. These effects were fully inhibited by CGP (0.3 microM) and AT (1.0 microM), inhibitors of beta 1AR but not by ICI (0.1 microM) a beta 2AR inhibitor. ZIN at relatively lower concentrations (< or = 0.1 microM) did not increase ICaL. CGP (0.3 microM) but not AT and ICI inhibited ICaL in the absence of beta AR agonists. CGP inhibition of ICaL was absent in the presence of forskolin (FK, 1.0 microM) that increases cAMP levels and ICaL by directly stimulating the adenylate cyclase. These indicate that none of the antagonists affect ICaL through an action downstream of beta AR.
beta-adrenergic agonists increase ICaL via beta 1AR but not beta 2AR in canine ventricular myocytes.
为了确定β1肾上腺素能受体（β1AR）和β2肾上腺素能受体（β2AR）亚型与L型钙电流（ICaL）的功能偶联，我们研究了非选择性激动剂异丙肾上腺素（ISO）以及相对选择性的β2AR激动剂齐帕特罗（ZIN）和沙丁胺醇（SAL）对分离的犬心室肌细胞中ICaL的影响，实验分别在存在和不存在选择性β1AR拮抗剂CGP 20712A（CGP）和阿替洛尔（AT）以及选择性β2AR拮抗剂ICI 118,551（ICI）的情况下进行。使用“膜片型”微电极和全细胞电压钳测定ICaL峰值。ISO（0.5微摩尔）使ICaL最大增加3.5±0.67倍。ZIN（10.0微摩尔）和SAL（10.0微摩尔）分别使ICaL最大增加1.5±0.2（n = 5）倍和1.4±0.1（n = 5）倍。这些作用被β1AR抑制剂CGP（0.3微摩尔）和AT（1.0微摩尔）完全抑制，但未被β2AR抑制剂ICI（0.1微摩尔）抑制。相对较低浓度（≤0.1微摩尔）的ZIN不会增加ICaL。在不存在βAR激动剂的情况下，CGP（0.3微摩尔）而非AT和ICI抑制ICaL。在存在可通过直接刺激腺苷酸环化酶增加环磷酸腺苷（cAMP）水平和ICaL的福斯可林（FK，1.0微摩尔）时，CGP对ICaL的抑制作用消失。这些表明，没有一种拮抗剂通过βAR下游的作用影响ICaL。
在犬心室肌细胞中，β肾上腺素能激动剂通过β1AR而非β2AR增加ICaL。
