Editors' ChoiceNeuroscience

The Sigma-1 Receptor—Orphan No More

Science Signaling  17 Feb 2009:
Vol. 2, Issue 58, pp. ec57
DOI: 10.1126/scisignal.258ec57

The sigma-1 receptor has long been fairly mysterious, originally identified as a molecule that binds opioid drugs and thought to be important in some psychiatric diseases and cocaine addiction. However, it has been an “orphan receptor” for years—lacking known endogenous ligands. Now Fontanilla et al. have used receptor binding, photoaffinity labeling and displacement, electrophysiology, and behavioral tests in knockout animals to demonstrate that the naturally occurring hallucinogen N,N-dimethyltryptamine (DMT) is the endogenous ligand for sigma-1 receptors.

D. Fontanilla, M. Johannessen, A. R. Hajipour, N. V. Cozzi, M. B. Jackson, A. E. Ruoho, The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator. Science 323, 934–937 (2009). [Abstract] [Full Text]