García-Sáinz J A, Alcántara R, Hernández-Sotomayor S M, Mas-Oliva J
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, D.F., México.
Life Sci. 1989;44(23):1767-75. doi: 10.1016/0024-3205(89)90564-x.
The beta-adrenergic responsiveness of hepatocytes obtained from hypothyroid rats and of a transplantable hepatoma cell line (AS-30D) were studied by measuring the accumulation of cyclic AMP. The potency order for agonists in hepatocytes was: isoproterenol greater than epinephrine much greater than norepinephrine whereas in the hepatoma cells the potency order was: isoproterenol greater than norepinephrine greater than or equal to epinephrine. The effect of isoproterenol was antagonized in hepatocytes by low concentrations of ICI 118551 and only partially by concentrations of atenolol as high as 100 microM. In hepatoma cells the effect of isoproterenol was inhibited by both antagonists with the potency order atenolol greater than ICI 118551. These data indicate that in hepatocytes the effect is mediated by beta 2-adrenoceptors whereas in hepatoma cells it is through beta 1-adrenoceptors. Preincubation of hepatoma cells with isoproterenol or phorbol-myristate-acetate diminished the subsequent beta-adrenergic responsiveness of the cells. Interestingly, when both isoproterenol and phorbol-myristate-acetate were present during the preincubation the beta-adrenergic desensitization observed was bigger than that induced by any of these agents alone.
通过测量环磷酸腺苷（cAMP）的积累，研究了从甲状腺功能减退大鼠获得的肝细胞以及一种可移植肝癌细胞系（AS - 30D）的β - 肾上腺素能反应性。在肝细胞中，激动剂的效力顺序为：异丙肾上腺素＞肾上腺素＞＞去甲肾上腺素；而在肝癌细胞中，效力顺序为：异丙肾上腺素＞去甲肾上腺素≥肾上腺素。低浓度的ICI 118551可拮抗异丙肾上腺素对肝细胞的作用，而高达100微摩尔浓度的阿替洛尔只能部分拮抗其作用。在肝癌细胞中，两种拮抗剂均可抑制异丙肾上腺素的作用，效力顺序为阿替洛尔＞ICI 118551。这些数据表明，在肝细胞中，该作用由β₂ - 肾上腺素能受体介导，而在肝癌细胞中则通过β₁ - 肾上腺素能受体介导。用异丙肾上腺素或佛波醇 - 肉豆蔻酸酯 - 乙酸盐预孵育肝癌细胞会降低细胞随后的β - 肾上腺素能反应性。有趣的是，当预孵育期间同时存在异丙肾上腺素和佛波醇 - 肉豆蔻酸酯 - 乙酸盐时，观察到的β - 肾上腺素能脱敏作用比单独使用任何一种药物诱导的都要大。
