Sarkar Pradip K, Biswas Avijit, Ray Arun K, Martin Joseph V
Department of Basic Sciences, Parker University, 2500 Walnut Hill Lane, Dallas, TX 75229, USA ; Center for Computational & Integrative Biology, Rutgers University, 315 Penn Street, Camden, NJ 08102, USA ; Department of Molecular Medicine, Bose Institute, P-1/12, CIT, Scheme VII-M, Calcutta 700054, India.
J Thyroid Res. 2013;2013:457953. doi: 10.1155/2013/457953. Epub 2013 Nov 7.
The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na(+)-K(+)-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na(+)-K(+)-ATPase activity (but not Mg(2+)-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3 and the β -adrenergic agonist isoproterenol inhibited Na(+)-K(+)-ATPase activity in cerebrocortical synaptosomes in similar ways, the β -adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na(+)-K(+)-ATPase activity in a dose-dependent manner, suggesting that the effect of T3 on synaptosomal Na(+)-K(+)-ATPase activity was independent of β -adrenergic receptor activation. The effect of T3 on synaptosomal Na(+)-K(+)-ATPase activity was inhibited by the α2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activate Gi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.
甲状腺激素（TH）在成年哺乳动物大脑正常功能中的作用尚不清楚。我们的研究已确定突触体钠钾ATP酶是成年大鼠大脑皮层中一种对TH有反应的生理参数。L-三碘甲状腺原氨酸（T3）和L-甲状腺素（T4）均以相似的剂量依赖性方式抑制钠钾ATP酶活性（但不抑制镁ATP酶活性），而TH的其他代谢产物作用较弱。尽管T3和β-肾上腺素能激动剂异丙肾上腺素以相似方式抑制脑皮质突触体中的钠钾ATP酶活性，但β-肾上腺素能受体阻滞剂普萘洛尔并未抵消T3的作用。相反，普萘洛尔以剂量依赖性方式进一步抑制钠钾ATP酶活性，这表明T3对突触体钠钾ATP酶活性的作用独立于β-肾上腺素能受体激活。T3对突触体钠钾ATP酶活性的作用被α2-肾上腺素能激动剂可乐定和谷氨酸抑制。值得注意的是，可乐定和谷氨酸均激活膜第二信使系统的Gi蛋白，提示这可能是抑制TH作用的一种潜在机制。在本文中，我们为成年条件下TH在神经元膜相关能量偶联信号转导过程中的非基因组作用机制提供了支持。
