Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
JIB
BioConferenceLive

New Understanding of Receptor Regulation Suggests Target for New Drugs

By BiotechDaily International staff writers
Posted on 09 Jan 2013
A study leading to improved understanding of G-protein coupled receptor regulation suggests a new set of targets for designing drugs to more effectively regulate this medically important family of receptors.

More than one-third of drugs on the market directly or indirectly regulate G protein-coupled receptors (GPCRs). Some indirect drugs trigger beta arrestins that downregulate activated GPCRs mainly by causing the receptors to be removed from the cell surface to be subsequently recycled or, via ubiquitination, degraded. The natural action of beta arrestins lowers the cell surface concentration of GPCRs and so can interfere with drugs designed to directly target GPCRs, in some cases leading to drug tolerance in patients and a need for using higher doses.

The current study, led by principal investigator Carlos E. Alvarez, PhD, at Nationwide Children's Hospital (Columbus, OH, USA), identified related GPCR regulatory roles by another subfamily of arrestins, the “alpha arrestins,” recently discovered by Dr. Alvarez’s laboratory. Using biochemical and imaging approaches, the researchers now found that alpha arrestins respond to ligand-bound receptor activation, and recruit enzymes that chemically modify the receptor to initiate aspects of down-regulation. Time course studies showed that these effects occur in the first 1-5 minutes after ligand activation, the same time frame that beta arrestins are known to trigger receptor downregulation. Using coimmunoprecipitation and co-localization methods, the researchers were also the first to find strong evidence suggesting that alpha arrestins function coordinately with beta arrestins.

"Our findings suggest that alpha arrestins, like beta arrestins, are ubiquitous regulators of G-protein coupled receptor signaling," said Dr. Alvarez. A major effort in current pharmacology is to develop drugs with functional selectivity that target either G protein or beta arrestin signaling effects. Dr. Alvarez foresees alpha arrestins becoming important in refining such efforts. "Just as has been discovered with beta blockers and beta arrestin, I expect we'll find drugs that also have significant alpha arrestin effects," said Dr. Alvarez.

The study was published online December 7, 2012, in the journal PLoS One.

Related Links:
Nationwide Children's Hospital




comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: Microcomputed tomography images (top) and histology images (bottom) of the knees of mice fed a very high fat diet containing omega-3 fatty acid supplement (left) or only omega-6 fatty acids (right) after a knee injury. The omega-6 diet showed abnormal bone remodeling and calcified tissue formation in the joint (white arrow). The omega-6 diet also showed significant loss of cartilage (red staining, yellow arrowhead) and increased joint inflammation (Photo courtesy of Duke University).

Dietary Omega-3 Fatty Acids Moderate Severity of Osteoarthritis in a Mouse Model

Researchers working with an osteoarthritis (OA) obese mouse model found that the fat content of the animals' diet contributed more to the development or arrest of OA than did body weight.... Read more

Therapeutics

view channel

Vaccine Being Developed for Heart Disease Close to Reality

The world’s first vaccine for heart disease is becoming a possibility with researchers demonstrating significant arterial plaque reduction in concept testing in mice. Klaus Ley, MD, from the La Jolla Institute for Allergy and Immunology (LA Jolla, CA, USA), and a vascular immunology specialist, is leading the vaccine... Read more

Business

view channel

A Surge in IPOs Revitalize Investments for the Global Pharma and Biotech

Anti-infective drugs, oncology, and pharmaceutical contract laboratories attract the most investment up to now. The intensified private equity and venture capital (PEVC) deal activity in the global healthcare industry during the recession years, 2008–2010, witnessed a waning post-2010. However, the decline in deals... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.