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  • Title: Effects of chronic administration of adenosine antagonists on adenosine A1 and A2a receptors in mouse brain.
    Author: Traversa U, Rosati AM, Florio C, Vertua R.
    Journal: In Vivo; 1994; 8(6):1073-8. PubMed ID: 7772740.
    Abstract:
    In the present study the effects of chronic in vivo treatments with caffeine and more selective antagonists (PACPX and PD115,199) on the binding parameters of 3H-CHA and 3H-NECA to cortical A1 and striatal A2a adenosine receptors of mouse brain are shown. The drugs were injected intraperitoneally once a day for 6 or 20 days. Treatment for 20 days with caffeine (250 mumol/kg), PD115,199 (50-250 nmol/kg) and PACPX (250 nmol/kg) shifted the A1 low affinity receptors into an agonist-specific high affinity state. Moreover, after 20 days of treatment, the antagonists decreased the affinity of 3H-CHA to A1 receptors in the high affinity state. Antagonist treatments for 6 days did not modify the 3H-CHA binding parameters. The A2a striatal receptors were dose- and time-dependently up-regulated by caffeine and PD115,199, whereas PACPX displayed an up-regulation independent of dose or length of treatment. Moreover, PD115,199 decreased the affinity of 3H-NECA to A2a striatal receptors. This effect on affinity was visible after 20 days of treatment with 50 and 250 nmol/kg. This study provides evidence for a sensitivity of A2a receptors greater than that of A1 receptors and for a different regulation of cortical A1 and striatal A2a adenosine receptors of mouse brain after chronic treatment with antagonists.
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