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A high-affinity cocaine binding site associated with the brain acid soluble protein 1.
Harraz, Maged M; Malla, Adarsha P; Semenza, Evan R; Shishikura, Maria; Singh, Manisha; Hwang, Yun; Kang, In Guk; Song, Young Jun; Snowman, Adele M; Cortés, Pedro; Karuppagounder, Senthilkumar S; Dawson, Ted M; Dawson, Valina L; Snyder, Solomon H.
Afiliação
  • Harraz MM; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Malla AP; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Semenza ER; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Shishikura M; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Singh M; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Hwang Y; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Kang IG; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Song YJ; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Snowman AM; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Cortés P; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Karuppagounder SS; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Dawson TM; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Dawson VL; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
  • Snyder SH; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A ; 119(16): e2200545119, 2022 04 19.
Article em En | MEDLINE | ID: mdl-35412917
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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Droga / Proteínas de Ligação a Calmodulina / Proteínas de Transporte / Cocaína / Proteínas do Citoesqueleto / Proteínas do Tecido Nervoso Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores de Droga / Proteínas de Ligação a Calmodulina / Proteínas de Transporte / Cocaína / Proteínas do Citoesqueleto / Proteínas do Tecido Nervoso Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2022 Tipo de documento: Article