Büscher R, Belger H, Eilmes K J, Tellkamp R, Radke J, Dhein S, Hoyer P F, Michel M C, Insel P A, Brodde O E
Institute of Pharmacology and Toxicology, University of Halle, Magdeburger Strasse 4, D-06097 Halle/Saale, Germany.
Pharmacogenetics. 2001 Apr;11(3):199-205. doi: 10.1097/00008571-200104000-00003.
beta 1-adrenoceptors play a pivotal role in regulating contractility and heart rate in the human heart. Recently, a polymorphism of the beta 1-adrenoceptor has been detected: at amino acid position 389 either Gly or Arg has been found with the Gly389 exhibiting reduced responsiveness upon agonist-induced stimulation in vitro. In order to find out whether the Gly389 polymorphism exhibits blunted responsiveness also in vivo we studied, in healthy volunteers, the effects of exercise on heart rate and heart rate-corrected duration of electromechanical systole (QS2c as a measure of inotropism) which, in humans, is mediated by beta 1-adrenoceptors stimulation. Twenty-four healthy volunteers (12 female, 12 male) homozygous for the Gly389 or Arg389 exercised on a bicycle in supine position (25, 50, 75 and 100 W for 5 min each), and heart rate and QS2c were assessed; in addition, plasma renin activity (PRA) was determined which is also regulated by beta 1-adrenoceptors in humans. Exercise caused work-load dependent increases in heart rate and PRA, and shortening of QS2c; however, these changes were not significantly different between the Gly389 and Arg389 polymorphism. Thus, these three beta 1-adrenoceptor responses did not differ between volunteers with the Arg389 versus the Gly389 polymorphism. Intragroup analysis, however, revealed that exercise induced increase in heart rate and shortening of QS2c were higher in female than in male volunteers. In conclusion, our data do not support the idea that the reduced responsiveness of Gly389 against agonist-induced stimulation observed in vitro is of major functional importance in vivo.
β1肾上腺素能受体在调节人体心脏的收缩力和心率方面起着关键作用。最近，已检测到β1肾上腺素能受体的一种多态性：在氨基酸位置389处，发现了甘氨酸（Gly）或精氨酸（Arg），其中Gly389在体外激动剂诱导刺激时表现出反应性降低。为了弄清楚Gly389多态性在体内是否也表现出反应迟钝，我们在健康志愿者中研究了运动对心率和心率校正的机电收缩期持续时间（QS2c，作为变力性的指标）的影响，在人体中，这是由β1肾上腺素能受体刺激介导的。24名Gly389或Arg389纯合的健康志愿者（12名女性，12名男性）仰卧位在自行车上锻炼（分别以25、50、75和100瓦的功率锻炼5分钟），并评估心率和QS2c；此外，还测定了血浆肾素活性（PRA），其在人体中也受β1肾上腺素能受体调节。运动导致心率和PRA随工作量增加，以及QS2c缩短；然而，这些变化在Gly389和Arg389多态性之间没有显著差异。因此，具有Arg389与Gly389多态性的志愿者之间这三种β1肾上腺素能受体反应没有差异。然而，组内分析显示，运动引起的女性志愿者心率增加和QS2c缩短比男性志愿者更高。总之，我们的数据不支持以下观点：在体外观察到的Gly389对激动剂诱导刺激的反应性降低在体内具有主要功能重要性。
