Featured Research

from universities, journals, and other organizations

Not All Mammals Vomit -- Or How To Study Emesis In Mice

Date:
October 2, 2002
Source:
Journal Of Clinical Investigation
Summary:
If biologists have learned anything over the past decade, it is how similar all mammals are at the genetic level. 95% of the genes found in mice are also found in humans, and we even share a significant amount of genes and genetic circuitries with creatures as different as fruit flies or puffer fish. This might not come as much of a surprise to physiologists who have long used animals to learn about basic mechanisms in organ function that are shared across vertebrates or mammals, but the extent of overlap is still impressive to most.

If biologists have learned anything over the past decade, it is how similar all mammals are at the genetic level. 95% of the genes found in mice are also found in humans, and we even share a significant amount of genes and genetic circuitries with creatures as different as fruit flies or puffer fish. This might not come as much of a surprise to physiologists who have long used animals to learn about basic mechanisms in organ function that are shared across vertebrates or mammals, but the extent of overlap is still impressive to most. In many areas of biomedical research, rats or mice are the animal model of choice. And while most researchers are aware that mice are not just furry little humans that walk on all fours, some fundamental differences surprise even experts. Among 10 scientists who identify themselves as mouse geneticists, only one was aware that mice (and in fact all rodents) lack a very fundamental behavior: they do not vomit.

While that in itself raises all sorts of interesting questions (for example about the evolution of vomiting, and its advantages and disadvantages for the survival of a species), it poses a very specific problem when one tries to use rodents to study a drug with side effects that include nausea and emesis (the medical term for vomiting).

Annette Robichaud and colleagues at Merck Frosst Centre for Therapeutic Research in Montreal, Quebec, have faced this problem while developing drugs that inhibit a class of enzymes called class 4 phosphodiesterases, or PDE4s. PDE4 inhibitors have promise for the treatment of airway inflammatory diseases such as asthma, but their therapeutic potential has been limited by side effects of nausea and emesis. These side effects are thought to be caused by inhibition of PDE4s outside the airways. The PDE4 subfamily is composed of 4 subtypes that are present in overlapping but distinct tissues of the body, and the hope is that it might be possible to develop subtype-specific inhibitors that are effective in the airways but do not interfere with PDE4 activity in other tissues.

As a step towards that goal, the researchers at Merck Frosst set out to determine which PDE4 subtype is mediating the emetic response. The most direct way to do so is to take advantage of genetically engineered mice that lack particular subtypes. However, since mice do not exhibit an emetic response, Robichaud and colleagues had to measure a different response that is thought to correlate with emesis in creatures like us that do vomit. Fortunately, such a surrogate response exists: PDE inhibitors reverse the anesthetic effects of a different class of drugs called alpha2-adrenoceptor agonists, and this is thought to act via the same mechanism as the unwanted side effects.

As Robichaud and colleagues report in the September 30 issue of the Journal of Clinical Investigation, by studying the inhibitors ability to reverse anesthesia in mice that lacked two of the PDE4 subtypes, PDE4B and PDE4D, they could infer that inhibition of PDE4D is what mediates much of the emetic response.

The next step will be the development of selective PDE4 inhibitors that do not interfere with PDE4D function. Such drugs would be predicted not to affect alpha2-adrenoceptor agonist-mediated anesthesia in mice. More importantly, and to vindicate this complicated approach to pre-clinical drug development, they will hopefully maintain the beneficial anti-inflammatory effects in human airways without causing human patients to feel sick and vomit.


Story Source:

The above story is based on materials provided by Journal Of Clinical Investigation. Note: Materials may be edited for content and length.


Cite This Page:

Journal Of Clinical Investigation. "Not All Mammals Vomit -- Or How To Study Emesis In Mice." ScienceDaily. ScienceDaily, 2 October 2002. <www.sciencedaily.com/releases/2002/10/021002065951.htm>.
Journal Of Clinical Investigation. (2002, October 2). Not All Mammals Vomit -- Or How To Study Emesis In Mice. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2002/10/021002065951.htm
Journal Of Clinical Investigation. "Not All Mammals Vomit -- Or How To Study Emesis In Mice." ScienceDaily. www.sciencedaily.com/releases/2002/10/021002065951.htm (accessed August 1, 2014).

Share This




More Plants & Animals News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Pyrenees Orphan Bear Cub Gets Brand New Home

Pyrenees Orphan Bear Cub Gets Brand New Home

AFP (Aug. 1, 2014) The discovery of a bear cub in the Pyrenees mountains made headlines in April 2014. Despire several attempts to find the animal's mother, the cub remained alone. Now, the Pyrenees Conservation Foundation has constructed an enclosure. Duration: 00:31 Video provided by AFP
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
Visitors Feel Part of the Pack at Wolf Preserve

Visitors Feel Part of the Pack at Wolf Preserve

AP (July 31, 2014) Seacrest Wolf Preserve on the northern Florida panhandle allows more than 10,000 visitors each year to get up close and personal with Arctic and British Columbian Wolves. (July 31) Video provided by AP
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