Gonzalez-Muñoz C, Fuente Teodomiro, Hernández-Cascales J
Department of Pharmacology, Medical School, University of Murcia, Spain.
Eur J Pharmacol. 2009 Apr 1;607(1-3):151-5. doi: 10.1016/j.ejphar.2009.02.029. Epub 2009 Feb 23.
The effects of salbutamol on contractility and cAMP levels were investigated in rat right ventricular myocardium. Salbutamol (1-300 microM), produced a concentration-dependent positive inotropic effect which was not affected by ICI 118551 (50 nM), a beta2-adrenoceptor antagonist but was abolished by CGP 20712A (1 microM) a beta1-adrenoceptor antagonist. However, in rats pretreated with pertussis toxin (30 microg/kg intraperitoneal injection) salbutamol increases contractility (Emax = 9.8 +/- 1.8%, - log EC50 = 6.25 +/- 0.07, n = 5). The combination of salbutamol + CGP 20712A, also produces a concentration-dependent enhancement of contractility (Emax = 43.0 +/- 7.5%, - log EC50 = 6.3 +/- 0.04, n = 6), in the presence of 30 microM of the non selective phosphodiesterase (PDE) inhibitor 3-isobutylmethylxantine (IBMX) which was prevented by ICI 118551 (50 nM). Also, salbutamol + CGP 20712A fail to increase cAMP tissue levels but enhance them in the presence of IBMX. This effect was also prevented by ICI 118551. These results indicate that PDEs blunt contractility and cAMP production mediated by beta2-adrenoceptors in rat ventricular myocardium. Gi protein, although less efficiently than PDEs, also limits inotropic effects of salbutamol mediated by beta2-adrenoceptors in this tissue.
在大鼠右心室心肌中研究了沙丁胺醇对收缩性和环磷酸腺苷（cAMP）水平的影响。沙丁胺醇（1 - 300微摩尔）产生浓度依赖性正性肌力作用，该作用不受β2肾上腺素能受体拮抗剂ICI 118551（50纳摩尔）影响，但被β1肾上腺素能受体拮抗剂CGP 20712A（1微摩尔）消除。然而，在用百日咳毒素（腹腔注射30微克/千克）预处理的大鼠中，沙丁胺醇增加收缩性（最大效应Emax = 9.8±1.8%，-log EC50 = 6.25±0.07，n = 5）。在存在30微摩尔非选择性磷酸二酯酶（PDE）抑制剂3 - 异丁基 - 1 - 甲基黄嘌呤（IBMX）的情况下，沙丁胺醇 + CGP 20712A的组合也产生浓度依赖性的收缩性增强（Emax = 43.0±7.5%，-log EC50 = 6.3±0.04，n = 6），ICI 118551（50纳摩尔）可阻止这种增强。此外，沙丁胺醇 + CGP 20712A未能增加组织中的cAMP水平，但在存在IBMX时可增强cAMP水平。ICI 118551也可阻止这种效应。这些结果表明，磷酸二酯酶抑制大鼠心室心肌中由β2肾上腺素能受体介导的收缩性和cAMP产生。Gi蛋白虽然作用效率低于磷酸二酯酶，但也限制了该组织中由β2肾上腺素能受体介导的沙丁胺醇的正性肌力作用。
