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

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: Alternative splicing produces two protein isoforms (Photo courtesy of Wikimedia Commons).

Key Regulator of Cancer-Inducing Alternative Splicing Identified

Cancer researchers have identified the splicing factor RBM4 (RNA-binding protein 4) as a key determinant in processes that prevent tumor development and spread. RBM4 is known to be crucial to gene splicing... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.