Calcium Entry Blockers: Autoradiographic Mapping of Their Binding Sites in Rat Brain

Abstract

This chapter discusses a possible functional role of organic calcium entry blockers in the brain, and performs receptor autoradiographic studies in this tissue, using ( +)-[ 3 H]PN200-110, ( ±)-[ 3 H]D600 and (-)-[ 3 H]D888 as ligands. The results of such studies can point to the brain areas that contain a high density of these sites that could then be used in the studies aimed at detecting a possible functional role of voltage-dependent calcium channels (VDCC) in the brain. It is observed in (+)-I3H] PN200-110 binding that dopaminergic or noradrenergic neurons, at least in the areas of their cell bodies, are perhaps not the prime candidates for the studies of a functional role of VDCC in the brain. The pharmacological properties as well as the pattern of the distribution of ( ±)-[3H]D600 binding sites, as revealed by receptor autoradiography, are difficult to reconcile with the proposal that ( ±)-[3H]D600, can be used in all the brain areas as a specific probe for the studies of the phenylalkylamine drug receptors of VDCC. It is observed that (-)-[ 3 H]D888 binding sites can be detected in all those brain areas that contain high affinity binding sites for (+)-[ 3 H]PN200-110.