[3H]tryptamine binding sites of rat cerebral cortex: pharmacological profile and plasticity

Equilibrium saturation analysis of the binding of [3H]tryptamine to membranes from the cerebral cortex of the rat at 0 degrees C indicated that [3H]tryptamine bound to a single class of high affinity binding sites (Kd = 1.29 +/- 0.13 nM). The binding of [3H]tryptamine was potently inhibited by tryptamine itself, beta-carboline, tetrahydro-beta-carboline and several beta-phenylethylamine derivatives. Structure-activity relationships of the beta-phenylethylamines tested showed that substitutions in para-position were the most potent with the following rank order of potency H less than OH less than Cl less than OCH3. Although chronic treatment with parachlorophenylalanine did not affect the parameters of the binding of [3H]tryptamine to cerebral cortical membranes of the rat, chronic treatment with clorgyline and deprenyl resulted in a 49% decrease in the density of binding sites for [3H]tryptamine, with no change in Kd. This modulation of the binding of [3H]tryptamine lends support to the proposal that binding sites for [3H]tryptamine could represent a specific class of receptors in the CNS. As such, the structure-activity relationships revealed within and between the various families of compounds tested provides useful information for the development of new chemical tools as potential agonists and/or antagonists at these sites.