Effect of free radicals on adenosine A(2A) and dopamine D2 receptors in the striatum of young adult and aged rats

Neurochemistry International
Tiago M AlfaroRodrigo A Cunha

Abstract

Parkinson's disease (PD) is a prevalent age-related motor dysfunction resulting from the hyperactivity of the indirect striatal pathway, which is controlled in an antagonistic manner by inhibitory dopamine D2 and facilitatory adenosine A(2A) receptors. Thus, dopamine precursors like l-DOPA are the standard therapy and A(2A) antagonists are now tested as anti-parkinsonians. Increased free radicals levels occur on aging and are proposed to be a contributing factor for PD. We now tested if free radicals affected A(2A) and D2 receptors in striatal membranes of young adult (2 months) and old (24 months) rats. The A(2A) receptor antagonist [3H]SCH 58261 bound to striatal membranes with a KD of 0.9 nM and a Bmax of 953 fmol/mg protein in young rats and with a KD of 0.8 nM and a Bmax of 725 fmol/mg protein in aged rats (24% decrease). The D2 receptor antagonist [3H]raclopride bound to striatal membranes with a KD of 4.0 nM and a Bmax of 598 fmol/mg protein in young rats and with a KD of 4.3 nM and a Bmax of 368 fmol/mg protein in aged rats (38% decrease). Exposure of striatal membranes to a free radical generation system (2 mM FeSO4 and 4 mM ascorbate) caused a similar decrease of [3H]SCH 58261 (35%) and [3H]raclopride (37%) binding in...Continue Reading

Citations

Nov 26, 2008·Nuclear Medicine and Biology·Shil Patel, Raymond Gibson
Feb 27, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Xiaoyun ZhouErik Fj de Vries
Jul 18, 2006·Pharmacology, Biochemistry, and Behavior·Lissiana Magna Vasconcelos AguiarGlauce Socorro B Viana
Nov 13, 2007·Neurobiology of Aging·Susanne RutzJean-Christophe Cassel
Sep 1, 2015·Pharmacological Reports : PR·Karol KramkowskiWlodzimierz Buczko

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