Mäki T, Kontula K, Härkönen M
Department of Clinical Chemistry, University of Helsinki, Meilahti Hospital, Finland.
Scand J Clin Lab Invest Suppl. 1990;201:25-43.
Catecholamines play an essential role in the activation of the cardiovascular system and in the regulation of energy metabolism in a variety of physiological conditions. Many of these effects are mediated through beta-adrenoceptors located on cell membranes. Binding of catecholamines to beta-adrenoceptor increases the concentration of intracellular cyclic AMP which in turn activates protein kinase A. This enzyme phosphorylates a number of other intracellular enzymes influencing cell metabolism and functions. The primary structures of the receptor and its topography in the cell membrane as well as its binding domains have been partially clarified. In studies of the human beta-adrenergic receptors blood lymphocytes have mostly been used as model cells. These cells carry receptors of mainly the beta 2-subtype. The adequacy of this model system has been demonstrated in several studies. In clinical work receptor assays have had limited use until now. However, studies on the pathophysiology of the adrenergic system in several diseases have revealed that receptor alterations may constitute an important factor in the disease process. Measurements of adrenergic receptors may also have increasing usefulness in determining optimal drug concentrations. Our own studies have primarily focused on physiological adjustments in the beta-adrenergic system during acute or prolonged physical exercise as well as receptor changes in heart failure, muscle diseases and the alcohol withdrawal syndrome. We have also explored receptor dynamics during therapy with beta-blocking agents. These studies, briefly reviewed in this communication, have led to the following conclusions: (1) High aerobic capacity is associated with an increased density and ability of lymphocytic beta-adrenoceptors to respond to catecholamines. (2) Both short-and long-term physical exercise induce a rapid up-regulation and more effective functioning of lymphocytic beta-adrenoceptors. (3) Administration of beta-blocking drugs is associated with a subnormal exercise-induced up-regulation and decreased functioning of the lymphocytic beta-adrenoceptors. (4) The exercise-provoked up-regulation and improved functioning of beta-adrenoceptors is blunted in heart failure patients. (5) Patients with Duchenne-type of muscular dystrophy have a reduced number of lymphocytic beta-adrenoceptors. (6) In chronic alcoholics the lymphocytic beta-adrenoceptor level is subnormal but during abrupt ethanol withdrawal a rapid increase in the number and functioning of the receptors to a normal level takes place. This sequence of events may lead to a condition of relative adrenergic hypersensitivity.
儿茶酚胺在多种生理状态下对心血管系统的激活以及能量代谢的调节中起着至关重要的作用。其中许多作用是通过位于细胞膜上的β-肾上腺素能受体介导的。儿茶酚胺与β-肾上腺素能受体结合会增加细胞内环状AMP的浓度，进而激活蛋白激酶A。这种酶会使许多其他细胞内酶磷酸化，从而影响细胞代谢和功能。受体的一级结构及其在细胞膜中的拓扑结构以及其结合域已部分阐明。在人类β-肾上腺素能受体的研究中，血液淋巴细胞大多被用作模型细胞。这些细胞主要携带β2-亚型受体。该模型系统的适用性已在多项研究中得到证实。在临床工作中，受体测定迄今应用有限。然而，对几种疾病中肾上腺素能系统病理生理学的研究表明，受体改变可能是疾病过程中的一个重要因素。肾上腺素能受体的测量在确定最佳药物浓度方面可能也会越来越有用。我们自己的研究主要集中在急性或长期体育锻炼期间β-肾上腺素能系统的生理调节以及心力衰竭、肌肉疾病和酒精戒断综合征中的受体变化。我们还探讨了β-阻滞剂治疗期间的受体动力学。本通讯简要回顾了这些研究，得出了以下结论：（1）高有氧能力与淋巴细胞β-肾上腺素能受体的密度增加以及对儿茶酚胺的反应能力增强有关。（2）短期和长期体育锻炼均可诱导淋巴细胞β-肾上腺素能受体快速上调并更有效地发挥功能。（3）给予β-阻滞剂与运动诱导的淋巴细胞β-肾上腺素能受体上调异常和功能降低有关。（4）心力衰竭患者运动引起的β-肾上腺素能受体上调和功能改善减弱。（5）杜兴氏型肌营养不良患者的淋巴细胞β-肾上腺素能受体数量减少。（6）慢性酒精中毒患者的淋巴细胞β-肾上腺素能受体水平低于正常，但在突然戒酒期间，受体数量和功能会迅速增加至正常水平。这一系列事件可能导致相对肾上腺素能超敏状态。
