title: Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors.
abstract: Cytoskeletal proteins are important in protein trafficking, membrane protein clustering, dendrite growth and the morphological maintenance of neurons. Sigma(1) receptors are unique endoplasmic reticular (ER) proteins that bind (+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Cocaine, via sigma(1) receptors, can cause the dissociation of a cytoskeletal adaptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P(3)] receptors on the ER as a sigma(1)-receptor-ankyrin complex, which then translocates to the plasma membrane and nucleus. The dissociation of sigma(1)-receptor-ankyrin from Ins(1,4,5)P(3) receptors also increases the intracellular Ca(2+) concentration [[Ca(2+)](i)], which affects the activity of cytoskeletal proteins. Furthermore, cocaine might increase [Ca(2+)](i) via phospholipase C (PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause life-long changes in neurons via cytoskeletal proteins by interacting with both D1 receptors and sigma(1) receptors.
authors.affiliation: Cellular Pathobiology Unit, Cellular Neurobiology Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. TSU@intra.nida.nih.gov
authors.forename: T P
authors.initials: TP
authors.lastname: Su
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D003042:Cocaine / Q000009:adverse effects*; D003598:Cytoskeletal Proteins / Q000187:drug effects* / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D006801:Humans; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017480:Receptors, sigma / Q000187:drug effects*; D000097605:Sigma-1 Receptor
chemical_list: D002118:Calcium; D003042:Cocaine; D003598:Cytoskeletal Proteins; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor