Examination of the relationship between the uptake system for 5-hydroxytryptamine and the high-affinity [3H]imipramine binding site--I. Inhibition by drugs.
The relationship between the binding site for imipramine and the uptake system for 5-hydroxytryptamine was examined. This was determined from the interaction between various drugs (including tricyclic antidepressants) and the high affinity accumulation of [3H]5-hydroxytryptamine in cortical synaptosomes from the rat, and with the high affinity binding of [3H]imipramine to cortical membranes of the rat. Imipramine and clomipramine, but not desipramine, were potent inhibitors of both binding of [3H]imipramine and the uptake of [3H]5-hydroxytryptamine. However, ouabain, panuramine and 5-hydroxytryptamine itself, all inhibited the binding of [3H]imipramine only at concentrations greater than those required to inhibit the uptake of [3H]5-hydroxytryptamine. Kinetic analysis revealed that inhibitors of the uptake system for 5-hydroxytryptamine produced inhibition by different mechanisms, but this did not account for their differential potency against uptake and binding. It is concluded that the binding site for [3H]imipramine and the uptake site for 5-HT are not directly linked and that drugs may inhibit the uptake of 5-HT at sites other than the binding site for [3H]imipramine.
D000818:Animals; D002352:Carrier Proteins; D002395:Catecholamines / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D007099:Imipramine / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism; D015031:Zimeldine / Q000494:pharmacology
D002352:Carrier Proteins; D002395:Catecholamines; D010880:Piperidines; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; C027775:imipramine receptor; D005473:Fluoxetine; C043858:panuramine; D012701:Serotonin; D015031:Zimeldine; D007099:Imipramine