Navigation Links
MDC and FMP researchers identify edema inhibitor
Date:4/5/2013

Researchers of the Max Delbrck 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 Klumann 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, doi:10.1681/ASN.2012030295)*.

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. Klumann.

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. Klumann 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. Klumann 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.


'/>"/>

Contact: Bachtler, Barbara
bachtler@mdc-berlin.de
49-309-406-3896
Helmholtz Association of German Research Centres
Source:Eurekalert

Related biology news :

1. Barrow researchers identify
2. Researchers discover brain cancer treatment using genetic material from bone marrow cells
3. Notre Dame researchers are using new technologies to combat invasive species
4. University of Montreal researchers discover how drug prevents aging and cancer progression
5. Researchers question evaluation methods for protected areas in the Amazon
6. Penn Researchers attach Lyme disease antibodies to nanotubes, paving way for diagnostic device
7. Researchers find novel mechanism regulating replication of insulin-producing beta cells
8. Researchers find novel way plants pass traits to next generation
9. Ludwig cancer researchers honored among first class of fellows in AACR Academy
10. Researchers issue forecast for moderate New England red tide in 2013
11. Researchers spot molecular control switch for preterm lung disorders
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/1/2016)... Canada , February 1, 2016 ... technological advancements to drive global touchfree intuitive gesture control ... --> Rising sales of consumer electronics coupled ... gesture control market size through ... consumer electronics coupled with new technological advancements to drive ...
(Date:1/25/2016)... BELL, Pa. , Jan. 25, 2016   Unisys Corporation ... recognition system at John F. Kennedy (JFK) International Airport, ... Border Protection (CBP) identify imposters attempting to enter ... do not belong to them. pilot testing of ... out initially at three terminals at JFK during January 2016. ...
(Date:1/20/2016)... 20, 2016 A market that just keeps ... from the explosion in genomics knowledge. Learn all about ... A range of dynamic trends are pushing market growth ... medicine - pharmacogenomics - pathogen evolution - next generation ... - greater understanding of the role of genetic material ...
Breaking Biology News(10 mins):
(Date:2/8/2016)... Novan, Inc. today announced that Director Robert A. Ingram ... In addition, Robert Keegan has been appointed to the ... --> North Carolina . ... of $32.8 million of net proceeds in a private Mezzanine B ... the Research Triangle area of North Carolina . ...
(Date:2/8/2016)... ... February 08, 2016 , ... ... of Semantic Graph Database technology, today announced the availability of AllegroGraph 6, the ... through the Cloudera Certified Technology Program (CCPT). AllegroGraph is the first ...
(Date:2/6/2016)... ... ... The Center for Excellence in Education (CEE) will sponsor a Bite of Science ... 2016. This Bite of Science session, hosted by the Smithsonian-Mason School of Conservation, ... in Front Royal, VA from 5:00 p.m. to 8:00 p.m. The dinner is for ...
(Date:2/5/2016)... February 5, 2016 Amarantus BioScience ... company focused on developing products for Regenerative Medicine, Neurology ... Pediatric Disease Designation (RPDD) from the US Food and ... MANF. MANF was previously granted orphan drug designation (ODD) ... Amarantus BioScience Holdings, Inc. (OTCQB: AMBS), ...
Breaking Biology Technology: