The behavioral effects of a selective A(3) adenosine receptor agonist
3-IB-MECA -6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice a
nd the localization of radioligand binding sites in mouse brain were e
xamined. Low levels A(3) adenosine receptors were detected in various
regions of the mouse brain (hippocampus, cortex, cerebellum, striatum)
, using a radioiodinated, high-affinity A(3)-agonist radioligand [I-12
5]AB-MECA do-4-aminobenzyl)-5'-N-methylcarboxamidoadenosine) Scatchard
analysis in the cerebellum showed that the K, value for binding to A(
3) receptors was 1.39 +/- 0.04 nM with a Bmax of 14.8 +/- 2.1 fmol/mg
protein. 3-IB-MECA at 0.1 mg/kg i.p. was a locomotor depressant with >
50% reduction in activity. Although selective A(1) or A(2), antagonist
s reversed locomotor depression elicited by selective A(1) or A(2a) ag
onists, respectively, the behavioral depressant effects of 3-IB-MECA w
ere unaffected. 3-IB-MECA also caused scratching in mice, which was pr
evented by coadministration of the histamine antagonist cyproheptadine
. The demonstration of a marked behavioral effect of A(3) receptor act
ivation suggests that the A(3) receptor represents a potential new the
rapeutic target.