Adenosine A1 receptor activation inhibits basal accumulation of inositol phosphates in rat hippocampus

The ability of the adenosine A(1) receptor selective agonist, N-6-cyclopentyladenosine, to modify basal accumulation of inositol phosphates in rat hippocampal slices, was investigated. Cyclopentyladenosine (10-300 nM) inhibited the basal accumulation of total [H-3]inositol phosphates, with an EC50 of 10 nM and an E-max of 24%. This effect of cyclopentyladenosine was prevented by the adenosine A(1) receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (30 nM). Cyclopentyladenosine (100 nM) also inhibited histamine (300 mu M)-stimulated accumulation of [H-3]inositol phosphates, this effect being quantitatively similar to that observed on basal [H-3]inositol phosphates accumulation. The results suggest that adenosine A(1) receptor activation is able, per se, to inhibit the formation of phosphatidylinositol-derived second messengers in hippocampus.