The binding of serotonin in brain: A study in vitro of the influence of physicochemical factors and drugs

Abstract

The binding of exogenous serotonin- 14C to a subcellular fraction (P 2) rich in nerve-endings from guinea pig brain was dependent upon the composition of the incubation medium, pH, temperature, concentration, and time. Further fractionation of the P 2 fraction by sucrose density methods showed that most of the binding was associated with the nerve-ending subfraction. Little or no binding occurred in the microsomal and mitochondrial fractions. The ruptured nerve-ending, synaptic vesicle, and supernatant fractions were prepared from the P 2 fraction by water treatment. At 37°, only 30 per cent of the original binding activity in the intact P 2 fraction was recovered in these three fractions, whereas at 2°, 80 per cent was found. The system in vitro was relatively specific for the binding of serotonin, since considerably less labeled histamine, tryptophan or norepinephrine was bound by the nerve-ending subfraction. The antidepressants, imipramine and iprindole (Wy-3263), reduced the binding of serotonin- 14C by more than 50 per cent in the nerve-ending subfraction. d-lysergic acid diethylamide (LSD) produced a 21 per cent reduction. Reserpine and iproniazid did not affect the binding.