Featured Research

from universities, journals, and other organizations

Researchers identify edema inhibitor: Substance that can prevent the accumulation of fluid in body tissue

Date:
April 5, 2013
Source:
Max Delbrück Center for Molecular Medicine
Summary:
Researchers in Germany have detected a substance that can prevent the accumulation of fluid in body tissue and thus edema formation. Their results could be important in the future for the treatment of excessive fluid retention in patients with chronic heart failure. The researchers have also discovered a new molecular mechanism controlling water homeostasis in the kidneys.

Renal principal cells with aquaporin-2 (blue) in the cell interior (image 1) and in the plasma membranes (image 2). The substance discovered by the MDC research group (4-acetyldiphyllin; image 3), prevents the redistribution of aquaporin-2 to the cell membrane. Nuclei are shown in green.
Credit: Immunofluorescence microscopy: Jana Bogum, Kerstin Zühlke, Burkhard Wiesner, Jenny Eichhorst/ Copyright: MDC/FMP

Researchers of the Max Delbrück Center for Molecular Medicine (MDC) and the Leibniz Institute of Molecular Pharmacology (FMP) in Berlin-Buch, Germany, have now detected a substance that can prevent the accumulation of fluid in body tissue and thus edema formation.

The results of Dr. Jana Bogum (MDC/FMP) from the MDC research group led by Professor Walter Rosenthal and PD Dr. Enno Klußmann could be important in the future for the treatment of excessive fluid retention in patients with chronic heart failure. Using a novel approach, the researchers have also discovered a new molecular mechanism controlling water homeostasis in the kidneys (Journal of the American Society of Nephrology).

Every day around 1 500 liters of blood flow through the kidneys. Of this total volume, the kidneys initially filter 180 liters of primary urine, which they concentrate to two liters and then excrete as the final urine. A key regulatory step of the concentration mechanism is the release of the hormone AVP (arginine-vasopressin) from the brain. This hormone triggers a multi-step signaling cascade in the kidneys which affects water channels (aquaporins) and in particular aquaporin-2. "The water channels, specifically aquaporin-2, and their redistribution play a key role in the regulation of the water balance," said Dr. Klußmann.

AVP, which is released from the brain upon thirst, induces aquaporin-2 located in the renal collecting duct principal cells to redistribute from the cell interior to the plasma membrane. The renal cells can then filter out the water from the primary urine flowing past the membrane via aquaporin-2. Dr. Klußmann explained: "To keep the renal cell from bursting and the body from dehydrating, the water is directed back via another group of water channels, aquaporin 3 and 4, into the bloodstream and body tissue. In contrast to aquaporin-2, these water channels are located in another domain of the plasma membrane in the renal principal cells and stay there permanently." Once the thirst is quenched, the levels of the hormone AVP are reduced and aquaporin-2 is shuttled back into the interior of the renal cell until it is needed again.

However, if the AVP level is too high, as is the case in patients with chronic heart failure, aquaporin-2 remains permanently in the plasma membrane of the renal principal cell and directs the water continuously from the primary urine into the renal collecting duct principal cells. These cells funnel the excess water into the body tissue. "This process contributes to edema," Dr. Klußmann said.

Discovery of how translocation of water channels can be inhibited

How can aquaporin-2 be prevented from settling permanently in the plasma membrane and thus triggering diseases or making them worse? Using a new research approach, the scientists were able to identify an inhibitor which prevents the translocation of the water channel aquaporin-2 into the cell membrane. At the same time they discovered a new regulatory mechanism of water homeostasis at the molecular level.

The researchers used "small molecules," low molecular weight organic compounds, which penetrate well into cells. They tested 17 700 such substances in renal cells and ultimately filtered out a substance that blocks the redistribution of aquaporin-2 to the plasma membrane. The substance (4-acetyldiphyllin) prevents phosphorylation, an important biological and regulatory activation step. In particular, the compound prevents a phosphorylation reaction that is catalyzed by a protein termed protein kinase A. This protein is activated in the signaling cascade that is triggered by AVP in the renal principal cells. In the presence of 4-acetyldiphillin protein kinase A cannot add a phosphate group to aquaporin-2, with the result that the water channels can no longer redistribute to the plasma membrane.

The new research findings may not only be of interest for the treatment of edema but also for the treatment of depression. Here, by contrast, medical researchers are seeking a way to shuttle aquaporin-2 to the plasma membrane of the renal principal cell, because lithium, which is often used to treat depression, prevents aquaporin-2 from redistributing to the plasma membrane, thus causing diabetes insipidus. If AVP is not released from the brain, or if the receptor for AVP in the renal cell is defective, this likewise results in diabetes insipidus, as Professor Rosenthal discovered several years ago. The affected individuals excrete 20 liters of urine every day. A similar effect, but not quite as drastic, is caused by alcohol. Drinking lots of beer causes the body to excrete large amounts of urine. The reason -- alcohol prevents the brain from releasing the hormone AVP and thus prevents the redistribution of aquaporin-2 to the plasma membrane.


Story Source:

The above story is based on materials provided by Max Delbrück Center for Molecular Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Bogum, D. Faust, K. Zuhlke, J. Eichhorst, M. C. Moutty, J. Furkert, A. Eldahshan, M. Neuenschwander, J. P. von Kries, B. Wiesner, C. Trimpert, P. M. T. Deen, G. Valenti, W. Rosenthal, E. Klussmann. Small-Molecule Screening Identifies Modulators of Aquaporin-2 Trafficking. Journal of the American Society of Nephrology, 2013; DOI: 10.1681/ASN.2012030295

Cite This Page:

Max Delbrück Center for Molecular Medicine. "Researchers identify edema inhibitor: Substance that can prevent the accumulation of fluid in body tissue." ScienceDaily. ScienceDaily, 5 April 2013. <www.sciencedaily.com/releases/2013/04/130405104814.htm>.
Max Delbrück Center for Molecular Medicine. (2013, April 5). Researchers identify edema inhibitor: Substance that can prevent the accumulation of fluid in body tissue. ScienceDaily. Retrieved July 28, 2014 from www.sciencedaily.com/releases/2013/04/130405104814.htm
Max Delbrück Center for Molecular Medicine. "Researchers identify edema inhibitor: Substance that can prevent the accumulation of fluid in body tissue." ScienceDaily. www.sciencedaily.com/releases/2013/04/130405104814.htm (accessed July 28, 2014).

Share This




More Health & Medicine News

Monday, July 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

$15B Deal on Vets' Health Care Reached

$15B Deal on Vets' Health Care Reached

AP (July 28, 2014) — A bipartisan deal to improve veterans health care would authorize at least $15 billion in emergency spending to fix a veterans program scandalized by long patient wait times and falsified records. (July 28) Video provided by AP
Powered by NewsLook.com
Traditional African Dishes Teach Healthy Eating

Traditional African Dishes Teach Healthy Eating

AP (July 28, 2014) — Classes are being offered nationwide to encourage African Americans to learn about cooking fresh foods based on traditional African cuisine. The program is trying to combat obesity, heart disease and other ailments often linked to diet. (July 28) Video provided by AP
Powered by NewsLook.com
West Africa Gripped by Deadly Ebola Outbreak

West Africa Gripped by Deadly Ebola Outbreak

AFP (July 28, 2014) — The worst-ever outbreak of the deadly Ebola epidemic grips west Africa, killing hundreds. Duration: 00:48 Video provided by AFP
Powered by NewsLook.com
Trees Could Save More Than 850 Lives Each Year

Trees Could Save More Than 850 Lives Each Year

Newsy (July 27, 2014) — A national study conducted by the USDA Forest Service found that trees collectively save more than 850 lives on an annual basis. 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