Synaptic and extrasynaptic localization of adenosine binding sites in the rat hippocampus.

In vitro binding sites for [125I]iodohydroxyphenylisopropyladenosine, an A1 adenosine agonist, were visualized in the CA1 area of the rat hippocampus by electron microscopical autoradiography. By fixing hippocampal slices after incubation in paraformaldehyde and osmium tetroxide, the specifically bound radioactive ligands were preferentially retained and cross-linked to the tissue. Autoradiographic silver grains were localized by a statistical evaluation according to the '50% probability circle analysis' and by measuring the distance of the grains from neighbouring membrane structures. A significant association of silver grains, indicating the presence of A1 adenosine receptors, was found at synaptic complexes and in addition at extrasynaptic sites on dendritic membranes. This suggests that modulation of nerve cell activity by adenosine involves synaptic as well as non-synaptic mechanisms.