A role for central A3‐adenosine receptors

FEBS Letters

Olah, Mark E.¹  Jacobson, Kenneth A.²  Nikodijević, Olga²  Daly, John W.²  Stiles, Gary L.¹  Shi, Dan²  Gallo-Rodriguez, Carola² 

[1] Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA;Laboratory of Bioorganic Chemistry, Natlonal Institute of Diabetes, and Digestive and Kidney Diseases, Natlonal Institutes of Health, Bethesda, MD 20892, USA

关键词: Adenosine receptor;    Xanthine;    Locomotor activity;    Histamine;    Radioligand binding;   

DOI  :  10.1016/0014-5793(93)81608-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The behavioral effects of a selective A₃ adenosine receptor agonist 3-IB-MECA (N ⁶-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice and the localization of radioligand binding sites in mouse brain were examined. Low levels of A₃ adenosine receptors were detected in various regions of the mouse brain (hippocampus, cortex, cerebellum, striatum), using a radioiodinated, high-affinity A₃-agonist radioligand [¹²⁵I]AB-MECA (N ⁶-(3-iodo-4-aminobenzyl)-5'-N-methylcarboxamidoadenosine). Scatchard analysis in the cerebellum showed that the K _d value for binding to A₃ receptors was 1.39 ± 0.04 nM with a B _max of 14.8 ±2.1 protein. 3-IB-MECA at 0.1 i.p. was a locomotor depressant with > 50% reduction in activity. Although selective A₁ or A_2a antagonists reversed locomotor depression elicited by selective A₁ or A_2a agonists, respectively, the behavioral depressant effects of 3-IB-MECA were unaffected. 3-IB-MECA also caused scratching in mice, which was prevented by coadministration of the histamine antagonist cyproheptadine. The demonstration of a marked behavioral effect of A₃ receptor activation suggests that the A₃ receptor represents a potential new therapeutic target.

【 授权许可】

Unknown