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Examination of the relationship between the uptake system for 5-hydroxytryptamine and the high-affinity [3H]imipramine binding site--I. Inhibition by drugs. 1986

M D Wood, and A M Broadhurst, and M G Wyllie

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.

UI MeSH Term Description Entries
D007099 Imipramine The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. Imidobenzyle,Imizin,4,4'-Methylenebis(3-hydroxy-2-naphthoic acid)-3-(10,11-dihydro-5H-dibenzo(b,f)azepin-5-yl)-N,N-dimethyl-1-propanamine (1:2),Imipramine Hydrochloride,Imipramine Monohydrochloride,Imipramine Pamoate,Janimine,Melipramine,Norchlorimipramine,Pryleugan,Tofranil
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D010880 Piperidines A family of hexahydropyridines.
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011955 Receptors, Drug Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified. Drug Receptors,Drug Receptor,Receptor, Drug
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002395 Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from TYROSINE. Catecholamine,Sympathin,Sympathins
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy

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