Characterization of the locomotor depression produced by an A2‐selective adenosine agonist

FEBS Letters

Jacobson, Kenneth A.¹  Nikodijević, Olga¹  Daly, John W.¹ 

[1] Laboratories of Chemistry and Bioorganic Chemistry, National Inst. of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Adenosine analog;    Locomotor depression;    Adenosine receptor;   

DOI  :  10.1016/0014-5793(90)80638-Y

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Adenosine analogs, such as N⁶-cyclohexyladenosine (CHA) that are selective for A₁-adenosine receptors, and analogs, such as 5'-N-ethylcarboxamidoadenosine (NECA) that are active at both a₁ and A₂ receptors, cause a profound depression of locomotor activity in mice via a central mechanism. The depression is effectively reversed by non-selective adenosine antagonists such as theophylline. We report that 2-[(2-aminoethyl-amino) carbonylethylphenylethylamino]-5'-N-ethylcarboxamidoadenosine (APEC), an amine derivative of the A₂ selective agonist, CGS21680, is a potent locomotor depressant in mice. The in vivo pharmacology is consistent with A₂-selectivity at a central site of action. Two parameters indicative of locomotor activity, horizontal activity and total distance travelled, were measured using a computerized activity monitor. From dose-respon- se curves it was found that APEC (ED₅₀ 16 ) is more potent than CHA (ED₅₀ 60 ) and less potent than NECA (ED₅₀ 2 ). The locomotor depression by APEC was reversible by theophylline, but not by the A₁-selective antagonists 8-cyclopentyltheophylline (CPT) and 8-cyclo-pentyl-1,3-dipropyl-2-thioxanthine, nor by the peripheral antagonists 8-p-sulfophenyltheophylline (8-PST) and 1,3-dipropyl-8-P-sulfophenylxanthine. The locomotor activity depression elicited by NECA and CHA was reversed by A₁-selective antagonists. These results suggest that the effects of APEC are due to stimulation of A₂ adenosine receptors in the brain.

【 授权许可】

Unknown