甲状腺激素和胺碘酮对培养的大鼠心肌细胞中β-肾上腺素能受体的调节作用

Regulation of beta-adrenoceptors by thyroid hormone and amiodarone in rat myocardiac cells in culture.

作者信息

Disatnik M H, Shainberg A

机构信息

Otto Meyerhoff Drug Receptor Center, Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.

出版信息

Biochem Pharmacol. 1991;41(6-7):1039-44. doi: 10.1016/0006-2952(91)90212-n.

DOI:10.1016/0006-2952(91)90212-n

PMID:1672592

Abstract

Hyperthyroidism is associated with elevation of heart cells sensitivity to catecholamines. We demonstrated that T3(10(-8) M) increased (30%) the number of beta-adrenoceptors in intact heart cells grown in vitro within 48 hr, without changing the affinity of the ligand [3H]CGP-12177. The increase in beta-adrenoceptors in T3-treated myocytes was not associated with an increase in receptor-mediated cAMP production. Amiodarone, an antiarrhythmic drug, reduces the sensitivity of the heart to catecholamines. To investigate this effect, we analysed the influence of amiodarone on the level of beta-adrenergic receptors. Ninety minute preincubation with amiodarone (5 x 10(-5) M) decreased the number of beta-adrenoceptors (35-50%) in intact heart cells and in heart membranes, without affecting the dissociation constants (Kd). Amiodarone inhibited isoproterenol induced cAMP production. These results indicate that the mechanism of action of amiodarone on the heart seems to be a non-competitive inhibition of catecholamine receptors.

摘要

甲状腺功能亢进与心肌细胞对儿茶酚胺的敏感性升高有关。我们证明，在体外培养的完整心肌细胞中，三碘甲状腺原氨酸（T3，10⁻⁸ M）在48小时内可使β-肾上腺素能受体数量增加（30%），而不改变配体[³H]CGP - 12177的亲和力。T3处理的心肌细胞中β-肾上腺素能受体的增加与受体介导的环磷酸腺苷（cAMP）生成增加无关。抗心律失常药物胺碘酮可降低心脏对儿茶酚胺的敏感性。为研究这种作用，我们分析了胺碘酮对β-肾上腺素能受体水平的影响。用胺碘酮（5×10⁻⁵ M）预孵育90分钟可使完整心肌细胞和心肌膜中的β-肾上腺素能受体数量减少（35 - 50%），而不影响解离常数（Kd）。胺碘酮抑制异丙肾上腺素诱导的cAMP生成。这些结果表明，胺碘酮对心脏的作用机制似乎是对儿茶酚胺受体的非竞争性抑制。