Na+-dependent binding sites for 3-H-mazindol or 3-H-cocaine are specifically located in dopaminergic nerve terminals of caudate nuclei and constitute a molecular component of the dopamine uptake domain. The Na+-dependent recognition sites for 3-H-cocaine in striatal synaptosomal membranes appear to be regulated by: (1) Receptor-receptor interaction involving corticofugal glutamatergic nerve endings; and by (2) GABA-modulin, a neuromodulatory protein present in synaptosomal membranes. Destruction of cortico-striatal glutamatergic nerve fibers increased the density of 3-H-cocaine and 3-H-mazindol binding sites in striatal synaptosomal membranes and increased the efficacy of cocaine or mazindol to inhibit 3-H- dopamine uptake in striatal slices. GABA-modulin decreased the number of the Na+-dependent binding sites of 3-H-cocaine indicating an allosteric receptor modulation.
