title: Effects of chronic administration of adenosine antagonists on adenosine A1 and A2a receptors in mouse brain.
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.
authors.affiliation: Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Trieste, Italy.
authors.forename: U
authors.initials: U
authors.lastname: Traversa
authors.forename: A M
authors.initials: AM
authors.lastname: Rosati
authors.forename: C
authors.initials: C
authors.lastname: Florio
authors.forename: R
authors.initials: R
authors.lastname: Vertua
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D011687:Purines / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation; D014970:Xanthines / Q000494:pharmacology*; D000096926:Benzenesulfonamides
chemical_list: D000241:Adenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D011687:Purines; D018047:Receptors, Purinergic P1; D013449:Sulfonamides; D014970:Xanthines; C052023:N-(2-(dimethylamino)ethyl)-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C027513:N(6)-cyclohexyladenosine; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine