Sigma-1 receptor's endogenous ligand is DMT

[Caduceus Mercurius]

Receptor's Binding Partner Identified
Shamans' hallucinogen that is also produced by the body binds to nervous system receptor

by Sophie L. Rovner

A hallucinogenic compound found in psychoactive snuffs and sacramental teas used in native shamanic rituals in South America has helped elucidate the role of a receptor found throughout the nervous system. The sigma-1 receptor was known to bind many synthetic compounds, and it was originally mischaracterized as a receptor for opioid drugs. But its real role in the body remains unknown. However, Arnold E. Ruoho of the University of Wisconsin, Madison, and colleagues have now solved one part of the mystery: They have discovered that the receptor's endogenous ligand is N,N-dimethyltryptamine (DMT) (Science 2009, 323, 934).

DMT is not only found in hallucinogenic teas and snuffs but is also produced by enzymes in the body. It's been detected in human urine, blood, and cerebrospinal fluid; in the mammalian lung; and in rodent brains. At least in rodents, DMT levels rise in stressful conditions. Ruoho's group found that DMT inhibits voltage-gated sodium ion channel activity when it binds to sigma-1 receptors on cells.

Chemical & Engineering News

 

[Nomada]

^ You got here some instances before me with the DMT news flash. Here, I found some more:

Psychoactive compound activates mysterious receptor
February 12th, 2009 in General Science / Chemistry

(PhysOrg.com) -- A hallucinogenic compound found in a plant indigenous to South America and used in shamanic rituals regulates a mysterious protein that is abundant throughout the body, University of Wisconsin-Madison researchers have discovered.

The finding, reported in the Feb. 13 issue of Science, may ultimately have implications for treating drug abuse and/or depression. Many more experiments will be needed, the researchers say.

Scientists have been searching for years for naturally occurring compounds that trigger activity in the protein, the sigma-1 receptor. In addition, a unique receptor for the hallucinogen, called dimethyltryptamine (DMT), has never been identified.

The UW-Madison researchers made the unusual pairing by doing their initial work the "old-fashioned," yet still effective, way. They diagrammed the chemical structure of several drugs that bind to the sigma-1 receptor, reduced them to their simplest forms and then searched for possible natural molecules with the same features. Biochemical, physiological and behavioral experiments proved that DMT does, in fact, activate the sigma-1 receptor.

"We have no idea at present if or how the sigma-1 receptor may be connected to hallucinogenic activity," says senior author Arnold Ruoho, chair of pharmacology at the UW-Madison School of Medicine and Public Health. "But we believe that the National Institute on Drug Abuse (NIDA) may be interested in biological mechanisms underlying psychoactive and addictive drug action."

In addition to being a component of psychoactive snuffs and sacramental teas used in native religious practices in Latin America, DMT is known to be present in some mammalian tissues, and it has also been identified in mammalian blood and spinal fluid. Elevated levels of DMT and a related molecule have been found in the urine of schizophrenics.

Ruoho speculates that the hallucinogen's involvement may mean that the sigma-1 receptor is connected in some fashion to psychoactive behavior. When his team injected DMT into mice known to have the receptor, the animals became hyperactive; mice in which the receptor had been genetically removed did not.

"Hyperactive behavior is often associated with drug use or psychiatric problems," says Ruoho. "It's possible that new, highly selective drugs could be developed to inhibit the receptor and prevent this behavior."

The study revealed an additional neurologic link by confirming that the sigma-1 receptor and some compounds that bind to it inhibit ion channels, which are important for nerve activity. Work by many researchers — including some from UW-Madison — initially showed this relationship in earlier studies.

Some studies have also linked the receptor to the action of antidepressant drugs, and National Institutes of Health (NIH) scientists recently found that it appears to serve as a "chaperon," helping proteins to fold properly.

The Wisconsin researchers found that DMT is derived from the naturally occurring amino acid tryptophan and is structurally related to the neurotransmitter serotonin. This finding, Ruoho says, illustrates the mantra often used in the biological processing of natural molecules: Nothing goes to waste.

"Our findings support the idea that biochemical alterations of molecules such as tryptophan can produce simple compounds such as DMT that may target other regulatory pathways served by sigma-1 receptors," he says.

DMT may also reflect the presence of an even larger family of natural compounds that arise from other structurally related amino acids that may further regulate the receptor, Ruoho adds.

"It may well be that these different, naturally derived chemical forms regulate the sigma-1 receptor in tissue and organ-specific ways," he says.

Source: University of Wisconsin-Madison

...

Link: http://www.physorg.com/news153670865.html

...couldn't find the author of the abstract though.

 

[Forkbender]

Interesting stuff.

"But we believe that the National Institute on Drug Abuse (NIDA) may be interested in biological mechanisms underlying psychoactive and addictive drug action."

I don't see the relation to addictive drug action.

 

[Alias55A]

neither do i, it could just mean they want to pull there leg to get more funding

 

[Rymmen]

never done DMT, myself... but i keep hearing about encountering with beings. the only other drug that i've encountered 'beings' is DXM, which also agonizes the sigma receptors.

maybe we've found a clue as to what it sort of kind of does?

 

[Bastiaan]

DMT is the best 8)

 

[Arlecchino]

The researchers surname ( Ruoho ) is Finnish and means weed and/or grass. Nice.

 

[endlessness]

I dont like the researchers attitude and the whole direction that they take and interpretation model.

"Ruoho speculates that the hallucinogen's involvement may mean that the sigma-1 receptor is connected in some fashion to psychoactive behavior. When his team injected DMT into mice known to have the receptor, the animals became hyperactive; mice in which the receptor had been genetically removed did not.

"Hyperactive behavior is often associated with drug use or psychiatric problems," says Ruoho. "It's possible that new, highly selective drugs could be developed to inhibit the receptor and prevent this behavior."

see? its always about making more money for the Big Pharma, stopping drug 'abuse' and stupid allegations of the sort. As if dmt was addictive, toxic or a problematic drug in any way

"Elevated levels of DMT and a related molecule have been found in the urine of schizophrenics. "

I thought that was debunked already.[/quote]

 

[Synthaesthetical]

Hello everybody, my first post on this forum.

Just as a note, DMT is not the only endogenous sigma-1 receptor ligand. DHEA is also one (1). There are also quite a few exogenous sigma-1 receptor ligands: methamphetamine, some ssris (zoloft and prozac), the kappa-opioid pentazocine (2).

The role of sigma-receptors is still quite a mystery. However I have read that it can confer significant neuroprotection against exitotoxicity.

1. Stimulation of Sigma-1 receptor signaling by dehydroepiandrosterone ameliorates pressure overload-induced hypertrophy and dysfunctions in ovariectomized rats. http://www.ingentaconnect.com/content/apl/ett/2009/00000013/00000011/art00001?crawler=true

2. Pharmacology and therapeutic potential of sigma(1) receptor ligands. http://www.ncbi.nlm.nih.gov/pubmed/19587856

 

[mriko]

As if dmt was addictive, toxic or a problematic drug in any way

I've read nothing about that in the article, but don't forget that DMT/beta-carbolines combinations can indeed suppress an addiction through some process that is yet to be defined.