The functioning neuronal transporter for dopamine: kinetic mechanisms and effects of amphetamines, cocaine and methylphenidate.
The dopamine transporter (DAT) is a transmembrane spanning protein that catalyzes the transport of dopamine across the neuronal membrane to concentrate the neurotransmitter inside the cell. Although the uptake of dopamine has been studied since the 1960s, more recent advances in knowledge of the protein itself and in making kinetically resolved measurements of its action have led to more insights into its mechanism and pharmacology. The literature of the kinetics of transporters and kinetic measurements of DAT activity is reviewed to provide an overview of the multisubstrate mechanism of DAT activity, its pharmacology with regard to amphetamine, cocaine and methylphenidate, and correlations of DAT activity with some behavioral outputs.
Schenk
James O
JO
Department of Chemistry, School of Molecular Biosciences, and Program in Pharmacology/Toxicology, Washington State University, Pullman, WA 99164-4630, USA. geni@wsu.edu
D000662:Amphetamines / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000493:pharmacokinetics* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008774:Methylphenidate / Q000493:pharmacokinetics* / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
D000662:Amphetamines; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; D008774:Methylphenidate; D003042:Cocaine