CENTRAL AND PERIPHERAL COCAINE RECEPTORS

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Abstract
High-affinity binding sites for [3H]cocaine {levo-[benzoyl-3,4-3H(N)]} were detected in membrane preparations from rat brain and liver. Analysis of binding to rat whole brain membranes revealed a high-affinity site (Kd = 16 nM) present at 0.65 pmol/mg of protein and a lower affinity site of (Kd = 660 nM) present at 5.1 pmol/mg of protein. The striatum had a much higher density of [3H]cocaine binding sites than either the frontal or occipital cortices. Also, the ratio of high/low affinity sites was highest for striatum, lower for cortices and lowest for whole brain. Scatchard analysis of cocaine binding to striatum and cortex suggested that, in addition to the high affinity binding (Kd = 16 nM), there were two or more lower affinity sites. Liver membranes bound [3H]cocaine with a single high affintiy (Kd = 1.7 nM) present at high concentrations (Bmax = 66 pmol/mg of protein). Binding of cocaine to both brain and liver membranes was sensitive to proteases, reduced by high Na+ concentrations (30-100 mM), eliminated by denaturing temperatures (i.e., 95.degree.C for 5 min) and optimal at pH 7.4. Binding of [3H]cocaine to the striatal and cortical synaptic membranes was inhibited by cocaine and analogs in the following decreasing rank order: (-)-cocaine > (-)-norcocaine > (-)cinnamoylcocaine > (+)-pseudococaine but (-)-ecgonine had no effect. The effective analogs also inhibited [3H]norepinephrine {levo[7-3H(N)]} and [3H]dopamine (dihydroxyphenylethylamine, 3,4-[7-3H]) uptake into cortical and striatal synaptosomes, respectively, with similar rank order. The data suggest that the dopamine and norepinephrine transporters may be involved in the central actions of cocaine.