Jackson D A, Nathanson N M
Department of Pharmacology, University of Washington, Seattle 98195-7750, USA.
J Biol Chem. 1995 Sep 22;270(38):22374-7. doi: 10.1074/jbc.270.38.22374.
Incubation of cultured embryonic chicken heart cells with the beta-adrenergic agonist isoproterenol resulted in a dose-dependent increase in the number of mAChR on the surface of intact cells. The isoproterenol-mediated increase in mAChR number was time dependent and reached a maximum by 48 h. Chick heart cells treated with isoproterenol exhibited a greater than 6-fold increase in the sensitivity for carbachol-mediated inhibition of adenylyl cyclase activity as compared to control. Stimulation of cultured heart cells for 24 h with isoproterenol resulted in a 25-35% increase in cm2 mRNA levels as compared to control cm2 mRNA levels. In contrast, the level of cm4 mRNA was not significantly affected by isoproterenol treatment. cm2 mRNA levels were maximally elevated by 15 h following isoproterenol stimulation and remained elevated for up to 72 h. Incubation of cells with isoproterenol in the presence of Rp-cAMP, an inhibitor of cAMP-dependent protein kinase, blocked the increase in the level of cm2 mRNA. Thus, prolonged activation of beta-adrenergic receptors results in an increase in mAChR number and muscarinic responsiveness in chick heart cells due to a cAMP-dependent protein kinase mediated increase in cm2 mRNA levels.
用β-肾上腺素能激动剂异丙肾上腺素培养鸡胚心脏细胞，完整细胞表面的毒蕈碱型乙酰胆碱受体（mAChR）数量呈剂量依赖性增加。异丙肾上腺素介导的mAChR数量增加具有时间依赖性，48小时时达到最大值。与对照组相比，用异丙肾上腺素处理的鸡心脏细胞对卡巴胆碱介导的腺苷酸环化酶活性抑制的敏感性增加了6倍以上。用异丙肾上腺素刺激培养的心脏细胞24小时，与对照cm2 mRNA水平相比，cm2 mRNA水平增加了25%-35%。相比之下，cm4 mRNA水平不受异丙肾上腺素处理的显著影响。异丙肾上腺素刺激后15小时，cm2 mRNA水平最高升高，并在长达72小时内保持升高。在存在cAMP依赖性蛋白激酶抑制剂Rp-cAMP的情况下，用异丙肾上腺素孵育细胞可阻断cm2 mRNA水平的升高。因此，β-肾上腺素能受体的长期激活导致鸡心脏细胞中mAChR数量和毒蕈碱反应性增加，这是由于cAMP依赖性蛋白激酶介导的cm2 mRNA水平增加所致。
