Open AccessA high-affinity cocaine binding site associated with the brain acid soluble protein 1
Author(s) -
Maged M. Harraz,
Adarsha P. Malla,
Evan R. Semenza,
Maria Shishikura,
Manisha Singh,
Yun Hwang,
In Guk Kang,
Young Jun Song,
Adele M. Snowman,
Pedro Cortés,
Senthilkumar S. Karuppagounder,
Ted M. Dawson,
Valina L. Dawson,
Solomon H. Snyder
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2200545119
Subject(s) - striatum , dopamine , nucleus accumbens , dopamine transporter , pharmacology , dopamine plasma membrane transport proteins , reuptake , chemistry , receptor , stimulant , dopamine receptor , neuroscience , biochemistry , biology , serotonin , dopaminergic
Significance Cocaine is a monoamine transport inhibitor. Current models attributing pharmacologic actions of cocaine to inhibiting the activity of the amine transporters alone failed to translate to the clinic. Cocaine inhibition of the dopamine, serotonin, and norepinephrine transporters is relatively weak, suggesting that blockade of the amine transporters alone cannot account for the actions of cocaine, especially at low doses. There is evidence for significantly more potent actions of cocaine, suggesting the existence of a high-affinity receptor(s) for the drug. Identifying and characterizing such receptors will deepen our understanding of cocaine pharmacologic actions and pave the way for therapeutic development. Here we identify a high-affinity cocaine binding site associated with BASP1 that is involved in mediating the drug’s psychotropic actions.