Martinez T T, McNeil J H
Can J Physiol Pharmacol. 1977 Feb;55(1):98-104. doi: 10.1139/y77-014.
In the isolated electrically driven rat atria, theophylline (5 X 10(-4)M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 X 10(-4) M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose-response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.
在离体电驱动大鼠心房中，茶碱（5×10⁻⁴M）使环磷酸腺苷（cAMP）含量有小幅但显著的增加，而利血平预处理可防止这种增加。还发现茶碱对利血平预处理动物的心房有直接收缩作用，此作用与cAMP无关。暴露于茶碱（5×10⁻⁴M）3分钟后，去甲肾上腺素的变力反应减弱，15分钟后增强，60分钟后消失。暴露于茶碱15分钟后，苯肾上腺素的最大变力反应无显著变化；然而，苯肾上腺素剂量-反应曲线略有左移。茶碱对cAMP的作用似乎与去甲肾上腺素和苯肾上腺素的反应具有相加性。在不同测试时间，茶碱对胺诱导的心脏cAMP和收缩力的作用表明，收缩作用与cAMP作用之间无相关性。结论是，茶碱在大鼠心房中的变力作用不是通过cAMP介导的；相反，甲基黄嘌呤可能通过钙代谢变化对心脏发挥作用。
