Featured Research

from universities, journals, and other organizations

Structure of ‘salvia’ receptor solved

Date:
March 21, 2012
Source:
University of North Carolina at Chapel Hill School of Medicine
Summary:
A research team has determined the structure of the kappa-opioid receptor—site of action of the widely abused hallucinogen Salvia divinorum – solving longstanding scientific mysteries and offering new insights for treating drug addiction, chronic pain and depression.

On the left panel is a Salvia divinorum plant. On the right panel, location of drug salvinorin A in the kappa opioid receptor.
Credit: Roth lab, UNC-Chapel Hill.

At the molecular level, drugs like salvinorin A (the active ingredient of the hallucinogenic plant Salvia divinorum) work by activating specific proteins, known as receptors, in the brain and body.

Salvinorin A, the most potent naturally occurring hallucinogen, is unusual in that it interacts with only one receptor in the human brain -- the kappa opioid receptor (KOR). Scientists know of four distinct types of opioid receptors, but until now the structure of the 'salvia receptor', and the details about how salvinorin A and other drugs interact with it, was a mystery.

In a research paper published March 21 in the journal Nature, scientists from the University of North Carolina at Chapel Hill, Scripps Research Foundation and two other institutions revealed the first-ever glimpse of the complete structure of the KOR. The finding could accelerate the development of new drugs to treat addiction, depression, anxiety, chronic pain and many other conditions.

"Once we see the structure of the receptor, it becomes easier for us to develop drugs that target the receptor in ways that might be beneficial for medical therapy," said Bryan Roth, MD, PhD, the Michael Hooker Distinguished Professor of Pharmacology at UNC and one of the paper's authors. "Drugs that block the receptor are potentially useful for treating a number of serious illnesses including chronic pain, cocaine addiction and other diseases."

The KOR is responsible for the action of drugs that affect human consciousness, awareness of pain and mood. The KOR is the only receptor that binds salvinorin A -- the active ingredient of the widely-abused hallucinogenic plant Salvia divinorum (also known as 'Magic mint', 'Salvia' and so on). Salvia use has surged among teenagers and young adults with more than 5 percent reporting usage in the past year.*

Knowing KOR's structure offers insights about how salvia and other drugs work. The finding also could help scientists design medicines that either activate or block KOR to benefit patients.

The research team crystallized KOR using JDTic, a drug currently in early-stage human trials; JDTic keeps KOR in an inactive state and blocks the actions of salvinorin A. In studies using animal models, JDTic has shown promise for treating cocaine and nicotine addiction, depression and anxiety.

The downside of JDTic and similar drugs targeting KOR is that they can exert their actions for weeks, whereas most prescribed medicines are cleared within 18-24 hours. "Now that we have the [KOR] structure, it opens up the possibility for us to make drugs that have the same action as JDTic but have better pharmaceutical properties," said Roth.

The research also resolves longstanding scientific debates about how drugs bind to KOR. The study found that compared to other receptors, the binding site on KOR is enormous, allowing drugs to bind to it in more than one way.

In addition, Roth said the research could help scientists develop drugs that activate KOR in the body without affecting the brain, which could be useful for treating chronic pain, kidney problems and many other disorders.

Co-authors include Eyal Vardy and Xi-Ping Huang at UNC-Chapel Hill; Huixian Wu, Daniel Wacker, Vsevolod Katritch, Mauro Mileni, Gye Won Han, Wei Liu, Aaron A. Thompson, Vadim Cherezov and Raymond C. Stevens from the Scripps Research Institute; F. Ivy Carroll and S. Wayne Mascarella from the Research Triangle Institute; and Richard B. Westkaemper and Philip D. Mosier from Virginia Commonwealth University.

The study was supported by funding from the National Institutes of Health.

* Source: National Institute on Drug Abuse InfoFacts; http://www.drugabuse.gov/publications/infofacts/salvia.


Story Source:

The above story is based on materials provided by University of North Carolina at Chapel Hill School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Huixian Wu, Daniel Wacker, Mauro Mileni, Vsevolod Katritch, Gye Won Han, Eyal Vardy, Wei Liu, Aaron A. Thompson, Xi-Ping Huang, F. Ivy Carroll, S. Wayne Mascarella, Richard B. Westkaemper, Philip D. Mosier, Bryan L. Roth, Vadim Cherezov, Raymond C. Stevens. Structure of the human κ-opioid receptor in complex with JDTic. Nature, 2012; DOI: 10.1038/nature10939

Cite This Page:

University of North Carolina at Chapel Hill School of Medicine. "Structure of ‘salvia’ receptor solved." ScienceDaily. ScienceDaily, 21 March 2012. <www.sciencedaily.com/releases/2012/03/120321142018.htm>.
University of North Carolina at Chapel Hill School of Medicine. (2012, March 21). Structure of ‘salvia’ receptor solved. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2012/03/120321142018.htm
University of North Carolina at Chapel Hill School of Medicine. "Structure of ‘salvia’ receptor solved." ScienceDaily. www.sciencedaily.com/releases/2012/03/120321142018.htm (accessed July 30, 2014).

Share This




More Mind & Brain News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

It's Not Just Facebook: OKCupid Experiments With Users Too

It's Not Just Facebook: OKCupid Experiments With Users Too

Newsy (July 29, 2014) If you've been looking for love online, there's a chance somebody has been looking at how you're looking. Video provided by Newsy
Powered by NewsLook.com
How Your Face Can Leave A Good Or Bad First Impression

How Your Face Can Leave A Good Or Bad First Impression

Newsy (July 29, 2014) Researchers have found certain facial features can make us seem more attractive or trustworthy. Video provided by Newsy
Powered by NewsLook.com
Losing Sleep Leaves You Vulnerable To 'False Memories'

Losing Sleep Leaves You Vulnerable To 'False Memories'

Newsy (July 27, 2014) A new study shows sleep deprivation can make it harder for people to remember specific details of an event. Video provided by Newsy
Powered by NewsLook.com
University Quiz Implies Atheists Are Smarter Than Christians

University Quiz Implies Atheists Are Smarter Than Christians

Newsy (July 25, 2014) An online quiz from a required course at Ohio State is making waves for suggesting atheists are inherently smarter than Christians. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins