Examination of the relationship between the uptake site for 5-hydroxytryptamine and the high affinity binding site for [3H]imipramine. II. The role of sodium ions.
Exogenous sodium ions stimulated both the high affinity binding of [3H]5-imipramine to membranes from the cortex of the rat and the high affinity accumulation of [3H]5-hydroxytryptamine (5-HT) into synaptosomes from the cortex of the rat with similar potencies. Imipramine and zimelidine inhibited synaptosomal uptake of [3H]5-HT potently in standard Tris-Krebs medium, but in a low-sodium medium their inhibitory potencies were significantly attenuated. The inhibitory potencies of panuramine and exogenous 5-HT on the uptake of [3H]5-HT were not significantly affected whether the uptake was measured in a normal or low-sodium Tris-Krebs. Imipramine and zimelidine were potent blockers of high affinity binding of [3H]imipramine whereas panuramine and 5-HT only inhibited the binding of [3H]imipramine at concentrations in excess of those required to inhibit the uptake of [3H]5-HT. It is suggested that imipramine inhibits the uptake of 5-HT by a sodium-dependent action probably at the high affinity binding site for [3H]imipramine, whereas panuramine and 5-HT inhibit the uptake of 5-HT by a sodium-independent mechanism at a site other than the binding site for [3H]imipramine.
D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D015031:Zimeldine / Q000494:pharmacology
D010880:Piperidines; C043858:panuramine; D012701:Serotonin; D015031:Zimeldine; D012964:Sodium; D007099:Imipramine; D009638:Norepinephrine