title: Mechanisms of L-triiodothyronine-induced inhibition of synaptosomal na(+)-k(+)-ATPase activity in young adult rat brain cerebral cortex.
abstract: 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.
authors.affiliation: 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.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Sarkar
authors.forename: Avijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ray
authors.forename: Joseph V
authors.initials: JV
authors.lastname: Martin