Featured Research

from universities, journals, and other organizations

Nerve Receptor Found To Be Key To Intestinal Inflammation

Date:
May 1, 2003
Source:
Duke University Medical Center
Summary:
Researchers at Duke University Medical Center have found that a specific nerve cell receptor appears to be necessary to initiate the development of inflammatory bowel disease (IBD), findings they believe could change how physicians treat this disorder.

DURHAM, N.C. -- Researchers at Duke University Medical Center have found that a specific nerve cell receptor appears to be necessary to initiate the development of inflammatory bowel disease (IBD), findings they believe could change how physicians treat this disorder.

The results of their studies, which were carried out in rats, could point toward a potential therapy aimed at blocking the receptor, known as vanilloid receptor type 1 (VR-1). Interestingly, they said, VR-1 is the receptor on sensory neurons that receives and transmits the "heat" and "pain" impulses felt when eating raw chili peppers.

The results of the Duke study were reported today (May 1, 2003) in the May issue of the journal Gut.

IBD is a general term given to a constellation of chronic disorders in which the intestine becomes inflamed, typically resulting in recurring abdominal cramps, pain and diarrhea, in some cases bloody. The cause of IBD is unknown, and it is believed that up to 2 million Americans suffer from this disorder, the researchers said.

"We know that immune modulators known as cytokines are responsible for the inflammation that is the hallmark of the disease, so research has focused on discovering a viral or bacterial trigger," said Christopher Mantyh, M.D., colorectal surgeon and senior member of the Duke team.

"However, our studies have shown that by blocking the VR-1 receptor, we can halt the development of IBD in an animal model," he continued. "So it would appear that the activation of the VR-1 receptor is the signal, or trigger, that 'revs up' the release of cytokines."

It has long been appreciated that sensory neurons within the intestinal system can play a role in the development of inflammation. Key to this process is Substance P, a neurotransmitter found in minute quantities in the human nervous system and intestines. It is primarily involved in the transmission of pain impulses and is also a potent pro-inflammatory mediator in the intestines.

"Studies have shown that using Substance P antagonists as well as denervation -- either surgical or chemically -- can block some forms of intestinal inflammation," Mantyh said. "However, what is missing is that trigger. What was not known was how the nerve cells in the intestine were stimulated to begin the inflammatory process."

In their experiments, the Duke team focused on the newly cloned VR-1 receptor, which can be activated by heat, acid and capsaicin, the ingredient that gives chili peppers their "heat."

Capsaicin stimulates the pain and heat response by binding, like a lock-and-key, to the VR-1 receptors on neurons. Just as long-time chili eaters find that prolonged consumption renders them immune to the peppers' effects, over-stimulation of VR-1 receptors can cause them to become desensitized.

The researchers used three groups of rats. The first group was administered capsaicin at birth, which chemically denervated them by "overstimulating' the VR-1 receptors to the point of inactivating them permanently. They were allowed to reach adulthood. The second group, which were adults, were given the agent capsazepine (CPZ), a VR-1 antagonists which blocks the receptor. The third group, the control, received no additional treatments.

The team then induced colitis, or intestinal inflammation, in all three groups of rats by giving them dextran sulphate sodium (DSS) in their water for a week. The animals' reactions to the treatment were carefully monitored and after one week, detailed studies were made of their intestinal tracts.

"In the control rats, DSS caused active colitis with its trademark ulceration of the intestinal lining," Mantyh said. "However, the two other groups showed significantly lower levels of disease. The treated rats were protected from the damaging effects of DSS administration. This data provides strong evidence that an animal model of colitis requires neurons containing VR-1.

"Inhibition of the VR-1 receptor in humans -- either by small doses of CPZ or other antagonists -- may represent a novel therapeutic pathway to prevent IBD," Mantyh continued.

The research was supported by grants from the National Institutes of Health, the American Surgical Association and the Department of Veterans Affairs.

Other members of the Duke team were Naoki Kihara, M.D., Sebastion de la Fiente, M.D., Kazunori Fujino, M.D., Toku Takahashi, D.M.D., and Theodore Pappas, M.D.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Nerve Receptor Found To Be Key To Intestinal Inflammation." ScienceDaily. ScienceDaily, 1 May 2003. <www.sciencedaily.com/releases/2003/05/030501075502.htm>.
Duke University Medical Center. (2003, May 1). Nerve Receptor Found To Be Key To Intestinal Inflammation. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2003/05/030501075502.htm
Duke University Medical Center. "Nerve Receptor Found To Be Key To Intestinal Inflammation." ScienceDaily. www.sciencedaily.com/releases/2003/05/030501075502.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. 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