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

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

doi:10.1073/pnas.2200545119

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	2200545119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	16
DOIs	https://doi.org/10.1073/pnas.2200545119
State	Published - Apr 19 2022

Keywords

BASP1
behavior
cocaine
drug abuse
receptor

ASJC Scopus subject areas

General

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10.1073/pnas.2200545119

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Harraz, M. M., Malla, A. P., Semenza, E. R., Shishikura, M., Singh, M., Hwang, Y., Kang, I. G., Song, Y. J., Snowman, A. M., Cortés, P., Karuppagounder, S. S., Dawson, T. M., Dawson, V. L., & Snyder, S. H. (2022). A high-affinity cocaine binding site associated with the brain acid soluble protein 1. Proceedings of the National Academy of Sciences of the United States of America, 119(16), Article 2200545119. https://doi.org/10.1073/pnas.2200545119

Harraz, MM, Malla, AP, Semenza, ER, Shishikura, M, Singh, M, Hwang, Y, Kang, IG, Song, YJ, Snowman, AM, Cortés, P, Karuppagounder, SS, Dawson, TM , Dawson, VL & Snyder, SH 2022, 'A high-affinity cocaine binding site associated with the brain acid soluble protein 1', Proceedings of the National Academy of Sciences of the United States of America, vol. 119, no. 16, 2200545119. https://doi.org/10.1073/pnas.2200545119

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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.",

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AU - Harraz, Maged M.

AU - Malla, Adarsha P.

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AU - Singh, Manisha

AU - Hwang, Yun

AU - Kang, In Guk

AU - Song, Young Jun

AU - Snowman, Adele M.

AU - Cortés, Pedro

AU - Karuppagounder, Senthilkumar S.

AU - Dawson, Ted M.

AU - Dawson, Valina L.

AU - Snyder, Solomon H.

PY - 2022/4/19

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N2 - 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.

AB - 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.

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

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