Effects of chronic administration of adenosine antagonists on adenosine A1 and A2a receptors in mouse brain
Traversa, U.; Rosati, A.M.; Florio, C.; Vertua, R.
In Vivo 8(6): 1073-1078
1994
ISSN/ISBN: 0258-851X PMID: 7772740 Document Number: 424414
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 A2-a 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 mu-mol/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 A2-a 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 A2-a 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 A2-a receptors greater than that of A1 receptors and for a different regulation of cortical A1 and striatal A2-a adenosine receptors of mouse brain after chronic treatment with antagonists.