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A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

ABSTRACT: Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine’s behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

SUBMITTER: Harraz MM

PROVIDER: S-EPMC9169839 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Harraz Maged M MM Malla Adarsha P AP Semenza Evan R ER Shishikura Maria M Singh Manisha M Hwang Yun Y Kang In Guk IG Song Young Jun YJ Snowman Adele M AM Cortés Pedro P Karuppagounder Senthilkumar S SS Dawson Ted M TM Dawson Valina L VL Snyder Solomon H SH

Proceedings of the National Academy of Sciences of the United States of America 20220411 16

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine’s behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-a ...[more]

PMID: 35412917

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Dataset Information

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Publications

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

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