Interactions of cations and anions with the binding of uptake blockers to the dopamine transporter
| Autor: | J.-J. Bonnet |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Anions
Tris Stereochemistry Dopamine transport Nerve Tissue Proteins Stimulation Dopamine agonist chemistry.chemical_compound Dopamine Uptake Inhibitors Dopamine Cations Membrane Transport Modulators medicine Animals Humans Dopamine transporter Pharmacology Dopamine Plasma Membrane Transport Proteins Binding Sites Membrane Glycoproteins biology Cell Membrane Sodium Membrane Transport Proteins Transporter chemistry biology.protein medicine.drug Binding domain |
| Zdroj: | European Journal of Pharmacology. 479:199-212 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2003.08.069 |
| Popis: | Uptake blockers and substrates are likely to recognise a common binding domain on the dopamine neuronal transporter (DAT). Among cations that form ionic gradients at the level of the cellular plasma membrane, Na + is the only one that can stimulate their binding. The binding stimulation appears over Na + concentrations ranging from 0 to 10–60 mM; at higher Na + concentrations, binding reaches a plateau or decreases, according to the uptake blocker that is studied. The majority of the other cations, including K + , Ca 2+ , Mg 2+ and Tris + , inhibit the binding of uptake blockers. Several metals impair binding to the DAT and/or the dopamine transport, but, under specific conditions, some of them, and chiefly Zn 2+ , stimulate binding. The complex relationships between cations, uptake blockers and the DAT suggest that cations recognise at least three different sites: the first one, site 1, is for cation-induced binding inhibition; the second one, site 2, is for Na + -induced binding stimulation; and the third one, site 3, is for Zn 2+ -induced binding stimulation. Modelling of the interactions between Na + , K + and radioligands allows a better understanding of the effects of cations at sites 1 and 2, and of uptake blockers at site 1. Some anions also facilitate the binding of uptake blockers to the DAT, as far as they are associated with Na + . The dependence of the binding of dopamine on ions could be involved in its preferential inward transport and used by uptake blockers for their own binding to the DAT. |
| Databáze: | OpenAIRE |
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