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Sodium Dependence of [ 3 H]]Paroxetine Binding and 5‐ [ 3 H]]Hydroxytryptamine Uptake in Rat Diencephalon
Author(s) -
Mann Catherine D.,
Hrdina Pavel D.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb11020.x
Subject(s) - chemistry , sodium , paroxetine , serotonin , serotonin plasma membrane transport proteins , serotonin transporter , binding site , binding potential , biochemistry , receptor , organic chemistry
The sodium dependence of binding of [ 3 H]]‐paroxetine, a selective serotonin uptake inhibitor, to the serotonin transporter in rat diencephalon was studied in both brain membranes and tissue sections and compared with that of 5‐ [ 3 H]]hydroxytryptamine ([ 3 H]]5‐HT) uptake by synaptosomes from the same region. Binding of [ 3 H]]‐paroxetine in both the membranes and sections displayed clear sodium dependence until a plateau occurring at 60 mMNaCl, the EC50 for sodium being 8 and 25 mM, respectively. The affinity (1/ K D ) of [ 3 H]]paroxetine binding was a simple hyperbolic function of sodium concentration. In contrast, the density of [ 3 H]]paroxetine sites was not affected by external Na + concentration. The uptake of [ 3 H]]5‐HT showed a similar pattern of sodium dependence with an EC 50 for Na + of 25 mM. Both the affinity (1/ K m ) and the rate (Vmax) of [ 3 H]]5‐HT uptake were dependent on external [Na + ] with sodium‐dependence curves fitting a rectangular hyperbola. The kinetic analysis of results indicates that one sodium ion is required for the binding of [ 3 H]]paroxetine as well as for the binding and translocation of each [ 3 H]]5‐HT molecule. The results concur with a single‐site model of the sodium‐dependent serotonin transporter with common or overlapping domains for 5‐HT and 5‐HT uptake inhibitors.