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The sigma1 receptor interacts with N-alkyl amines and endogenous sphingolipids

Ramachandran, S. and Chu, U.B. and Mavlyutov, T.A. and Pal, A. and Pyne, S. and Ruoho, A.E. (2009) The sigma1 receptor interacts with N-alkyl amines and endogenous sphingolipids. European Journal of Pharmacology, 609 (1-3). pp. 19-26. ISSN 0014-2999

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Abstract

The sigma1 receptor is distinguished for its ability to bind various pharmacological agents including drugs of abuse such as cocaine and methamphetamine. Some endogenous ligands have been identified as putative sigma1 receptor regulators. High affinity ligands for the sigma1 receptor contain a nitrogen atom connected to long alkyl chains. We found that long alkyl chain primary amines including endogenous amines belonging to the sphingolipid family such as d-erythro-sphingosine and sphinganine bind with considerable affinity to the sigma1 receptor but not to the sigma2 receptor. The binding of d-erythro-sphingosine to the sigma1 receptor appears to be competitive in nature as assessed against the radioligand [3H]-(+)-pentazocine. Interestingly, the well studied sphingolipid mediator sphingosine-1 phosphate did not bind to the sigma1 or the sigma2 receptor. Sphingosine is converted to sphingosine-1 phosphate by a family of sphingosine kinases that regulate the relative levels of these two bioactive lipids in the cell. The selective binding of sphingosine but not sphingosine-1 phosphate to the sigma1 receptor suggests a mechanism for regulation of sigma1 receptor activity by the sphingosine kinase. We have successfully reconstituted this hypothetical model in HEK-293 cells overexpressing both the sigma1 receptor and sphingosine kinase-1. The data presented here strongly supports sphingosine as an endogenous modulator of the sigma1 receptor.

Item type: Article
ID code: 19154
Keywords: sigma1 receptor, sphingolipid, alkyl amine, ligand binding, endogenous ligand, Pharmacy and materia medica
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Strathprints Administrator
    Date Deposited: 21 May 2010 16:11
    Last modified: 12 Mar 2012 11:12
    URI: http://strathprints.strath.ac.uk/id/eprint/19154

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