Strain-related differences in adenosine receptor density and in behavioral sensitivity to adenosine analogs in mice.
The behavioral effects of the adenosine agonists 5'-N-ethylcarboxamidoadenosine (NECA) was investigated in two strains of inbred mice, CD1 and CBA. NECA dose dependently reduced spontaneous locomotor activity with similar potency (ED50 = 36 +/- 1.5 and 36 +/- 1.1 nmol/kg IP for CBA and CD1 mice, respectively) and efficacy (> 90% at 100 nmol/kg) in the two strains. One nmol/kg NECA, an ineffective dose in CBA mice, exerted a significant stimulant action in CD1 mice. In saturation experiments, no differences were found in the density or in the affinity of striatal A2a receptors labeled with [3H]NECA. A strain-related difference was found in the density of striatal A1 receptors labeled with [3H]CCPA. In CBA mice, the Bmax value was 32% less than in CD1 mice (0.646 +/- 0.037 and 0.951 +/- 0.073 pmol bound/mg protein, respectively, p < 0.05). No differences in [3H]CCPA binding parameters were found in cortical and hippocampal membranes obtained from the two strains, whereas a higher density of A1 binding sites was found in the cerebellum of CBA mice. The present results show a close correlation between binding studies and the depressant action of NECA and present evidence for strain-related differences in regional distribution of central adenosine receptors and in behavioral response to purinergic drugs.
Florio
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C
Institute of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Trieste, Italy.
Rosati
A M
AM
Traversa
U
U
Vertua
R
R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013045:Species Specificity; D013806:Theophylline / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D019830:Adenosine-5'-(N-ethylcarboxamide); D013806:Theophylline; D000241:Adenosine