Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors.
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.
Su
T P
TP
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
Hayashi
T
T
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
D002118:Calcium; D003042:Cocaine; D003598:Cytoskeletal Proteins; D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor