Buschmans E, Hearse D J, Manning A S
Can J Cardiol. 1985 Nov-Dec;1(6):385-94.
The new inotropic agent, forskolin, is thought to act by stimulation of adenyl cyclase at a site remote from the beta-receptor. In this study we have characterized the action of forskolin in isolated, perfused rat and guinea-pig hearts. In both species, forskolin increased heart rate, left ventricular pressure and tissue cyclic AMP in a concentration-dependent manner. Significant responses were obtained with a minimum concentration of 2 X 10(-9)M forskolin in the rat and 2 X 10(-8)M in the guinea-pig. In both species maximal effects were observed with 2 X 10(-6)M forskolin. For any given forskolin concentration, the increases in cyclic AMP were greater in the rat heart than in the guinea-pig heart. In the rat heart, two beta-adrenoceptor blocking agents (1.6 X 10(-6)M propranolol or 2.6 X 10(-6)M timolol) were both able to reduce the increases in function and tissue cyclic AMP content caused by forskolin (2 X 10(-7) and 2 X 10(-8)M). However, no inhibition by beta-blockade was observed in hearts from catecholamine-depleted (reserpinized) animals or in hearts treated with high concentrations (2 X 10(-6)M) of forskolin. These results indicate that catecholamines may in some way be able to potentiate the actions of forskolin.
新型强心剂福斯高林被认为是通过刺激远离β受体的位点上的腺苷酸环化酶来发挥作用的。在本研究中，我们已对福斯高林在离体灌注的大鼠和豚鼠心脏中的作用进行了表征。在这两个物种中，福斯高林均以浓度依赖性方式增加心率、左心室压力和组织环磷酸腺苷（cAMP）。在大鼠中，最低浓度为2×10⁻⁹M的福斯高林以及在豚鼠中最低浓度为2×10⁻⁸M的福斯高林均可产生显著反应。在这两个物种中，2×10⁻⁶M的福斯高林均观察到最大效应。对于任何给定的福斯高林浓度，大鼠心脏中环磷酸腺苷的增加幅度均大于豚鼠心脏。在大鼠心脏中，两种β肾上腺素能受体阻滞剂（1.6×10⁻⁶M普萘洛尔或2.6×10⁻⁶M噻吗洛尔）均能够降低由福斯高林（2×10⁻⁷和2×10⁻⁸M）引起的功能和组织环磷酸腺苷含量的增加。然而，在儿茶酚胺耗竭（利血平化）动物的心脏中或在用高浓度（2×10⁻⁶M）福斯高林处理的心脏中未观察到β受体阻滞剂的抑制作用。这些结果表明，儿茶酚胺可能在某种程度上能够增强福斯高林的作用。
