Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 323 (5916): 934-937

Copyright © 2009 by the American Association for the Advancement of Science

The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

Dominique Fontanilla,1 Molly Johannessen,2 Abdol R. Hajipour,3 Nicholas V. Cozzi,1 Meyer B. Jackson,2 Arnold E. Ruoho1*

Abstract: The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.

1 Department of Pharmacology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
2 Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA.
3 Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, IR Iran.

* To whom correspondence should be addressed. E-mail: aeruoho{at}wisc.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Lifetime of UDP-galactose:Ceramide Galactosyltransferase Is Controlled by a Distinct Endoplasmic Reticulum-associated Degradation (ERAD) Regulated by Sigma-1 Receptor Chaperones.
T. Hayashi, E. Hayashi, M. Fujimoto, H. Sprong, and T.-P. Su (2012)
J. Biol. Chem. 287, 43156-43169
   Abstract »    Full Text »    PDF »
{sigma}-1 Receptor at the Mitochondrial-Associated Endoplasmic Reticulum Membrane Is Responsible for Mitochondrial Metabolic Regulation.
K.-S. C. Marriott, M. Prasad, V. Thapliyal, and H. S. Bose (2012)
J. Pharmacol. Exp. Ther. 343, 578-586
   Abstract »    Full Text »    PDF »
The Sigma-1 Receptor Binds to the Nav1.5 Voltage-gated Na+ Channel with 4-Fold Symmetry.
D. Balasuriya, A. P. Stewart, D. Crottes, F. Borgese, O. Soriani, and J. M. Edwardson (2012)
J. Biol. Chem. 287, 37021-37029
   Abstract »    Full Text »    PDF »
The sigma-1 receptor: a molecular chaperone for the heart and the soul?.
H. Ehmke (2012)
Cardiovasc Res 93, 6-7
   Full Text »    PDF »
Late-Onset Inner Retinal Dysfunction in Mice Lacking Sigma Receptor 1 ({sigma}R1).
Y. Ha, A. Saul, A. Tawfik, C. Williams, K. Bollinger, R. Smith, M. Tachikawa, E. Zorrilla, V. Ganapathy, and S. B. Smith (2011)
Invest. Ophthalmol. Vis. Sci. 52, 7749-7760
   Abstract »    Full Text »    PDF »
Sig1R Protein Regulates hERG Channel Expression through a Post-translational Mechanism in Leukemic Cells.
D. Crottes, S. Martial, R. Rapetti-Mauss, D. F. Pisani, C. Loriol, B. Pellissier, P. Martin, E. Chevet, F. Borgese, and O. Soriani (2011)
J. Biol. Chem. 286, 27947-27958
   Abstract »    Full Text »    PDF »
In Vivo Long-Term Kinetics of Radiolabeled N,N-Dimethyltryptamine and Tryptamine.
A. A. Vitale, A. B. Pomilio, C. O. Canellas, M. G. Vitale, E. M. Putz, and J. Ciprian-Ollivier (2011)
J. Nucl. Med. 52, 970-977
   Abstract »    Full Text »    PDF »
TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity.
F. G. Revel, J.-L. Moreau, R. R. Gainetdinov, A. Bradaia, T. D. Sotnikova, R. Mory, S. Durkin, K. G. Zbinden, R. Norcross, C. A. Meyer, et al. (2011)
PNAS 108, 8485-8490
   Abstract »    Full Text »    PDF »
Antagonist action of progesterone at {sigma}-receptors in the modulation of voltage-gated sodium channels.
M. Johannessen, D. Fontanilla, T. Mavlyutov, A. E. Ruoho, and M. B. Jackson (2011)
Am J Physiol Cell Physiol 300, C328-C337
   Abstract »    Full Text »    PDF »
Detergent-Resistant Microdomains Determine the Localization of {sigma}-1 Receptors to the Endoplasmic Reticulum-Mitochondria Junction.
T. Hayashi and M. Fujimoto (2010)
Mol. Pharmacol. 77, 517-528
   Abstract »    Full Text »    PDF »
Regulation of {sigma}-1 Receptors and Endoplasmic Reticulum Chaperones in the Brain of Methamphetamine Self-Administering Rats.
T. Hayashi, Z. Justinova, E. Hayashi, G. Cormaci, T. Mori, S.-Y. Tsai, C. Barnes, S. R. Goldberg, and T.-P. Su (2010)
J. Pharmacol. Exp. Ther. 332, 1054-1063
   Abstract »    Full Text »    PDF »
Sigma-1 Receptors Regulate Bcl-2 Expression by Reactive Oxygen Species-Dependent Transcriptional Regulation of Nuclear Factor {kappa}B.
J. Meunier and T. Hayashi (2010)
J. Pharmacol. Exp. Ther. 332, 388-397
   Abstract »    Full Text »    PDF »
Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1{middle dot}GTP pathway.
S.-Y. Tsai, T. Hayashi, B. K. Harvey, Y. Wang, W. W. Wu, R.-F. Shen, Y. Zhang, K. G. Becker, B. J. Hoffer, and T.-P. Su (2009)
PNAS 106, 22468-22473
   Abstract »    Full Text »    PDF »
Voltage-gated sodium channel modulation by {sigma}-receptors in cardiac myocytes and heterologous systems.
M. Johannessen, S. Ramachandran, L. Riemer, A. Ramos-Serrano, A. E. Ruoho, and M. B. Jackson (2009)
Am J Physiol Cell Physiol 296, C1049-C1057
   Abstract »    Full Text »    PDF »
When the Endogenous Hallucinogenic Trace Amine N,N-Dimethyltryptamine Meets the Sigma-1 Receptor.
T.-P. Su, T. Hayashi, and D. B. Vaupel (2009)
Science Signaling 2, pe12
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882