[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.
D000818:Animals; D001665:Binding Sites; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012642:Selegiline / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000378:metabolism*
D002243:Carbolines; D010627:Phenethylamines; D014363:Tryptamines; D012642:Selegiline; C029261:phenethylamine; C030820:tryptamine; C009804:tryptoline; D003010:Clorgyline