Heterogeneity of antidepressant binding sites on the recombinant rat serotonin transporter SERT1.

Article Details

Citation

Schloss P, Betz H

Heterogeneity of antidepressant binding sites on the recombinant rat serotonin transporter SERT1.

Biochemistry. 1995 Oct 3;34(39):12590-5.

PubMed ID
7548008 [ View in PubMed
]
Abstract

Antidepressant drugs block the uptake of serotonin into serotonergic nerve terminals and blood platelets. Here, binding of the tricyclic antidepressant [3H]imipramine to the recombinant rat serotonin transporter SERT1 expressed in human embryonic kidney cells was found to be nonhomogeneous. Scatchard analysis and competition experiments revealed the existence of two distinct antidepressant binding sites. At site 1, [3H]imipramine binding was strictly sodium-dependent with an apparent KD of approximately 10 nM. In contrast, [3H]imipramine binding to site 2 occurred also in the absence of sodium and exhibited a lower affinity. Binding of the nontricyclic antidepressant [3H]citalopram was observed only at site 2. The natural substrate of this carrier, serotonin, competitively inhibited antidepressant binding at both sites; however, its affinity to site 2 was approximately 5-fold lower. These data provide a molecular explanation for the distinct pharmacological actions of different antidepressants.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
ImipramineSodium-dependent serotonin transporterProteinHumans
Yes
Inhibitor
Details