EFFECTS OF DIVALENT-CATIONS ON ADENOSINE AGONIST BINDING TO A1 RECEPTORS AND NON-A1 NON-A2 SITES IN RAT CEREBRAL-CORTEX

In the present study results are reported concerning the effects of se veral divalent cations on the binding characteristics of [H-3]-cyclohe xyladenosine on A1 adenosine receptors and of [H-3]-N-ethylcarboxamido adenosine on non-A1/non-A2 sites in membranes from cerebral cortex of the rat. The [H-3]-cyclohexyladenosine binding to A1 receptors was dos e-dependently increased by Mn2+, Co2+, Ca2+. The binding characteristi cs of the agonist were differently affected by Ca2+/Mn2+ and Mg2+. Ca2 + and Mn2+ increased the B-max value without any change in K-d, wherea s Mg2+ decreased the K-d value without changing the B-max. In the pres ence of Ca2+ and Mg2+ the K-d value was similar to that obtained in th e presence of Mg2+, whereas the B-max value was similar to the apparen t number of binding sites calculated in the presence of Ca2+. The cati ons, Cu2+, Cd2+, Zn2+, decreased the A1 binding with IC50 values of 19 .6 mu M 39.2 mu M and 103.9 mu M, respectively. The binding characteri stics of [H-3]-N-ethylcarboxamidoadenosine to non-A1/non-A2 sites were affected by Ca2+, Mn2+, Co2+ and Mg2+ in the opposite manner to A1 re ceptors. They decreased the binding with IC50 values of 20.1 mM, 22.8 mM, 93.0 18.1 mM, respectively. This occurs through an enhancement in K-d values without changes in the number of binding sites. The finding s on A1 receptor and non-A1/non-A2 binding site, taken together, sugge st that cations could also exert a modulatory action via specific inte ractions with divalent cation binding sites on the receptor molecule.