Navigation Links
Study identifies potential new pathway for drug development
Date:12/10/2012

A newly found understanding of receptor signaling may have revealed a better way to design drugs. A study from Nationwide Children's Hospital suggests that a newly identified group of proteins, alpha arrestins, may play a role in cell signaling that is crucial to new drug development. The study appears in PLOS ONE.

More than one-third of drugs on the market work by targeting G protein-coupled receptors that control how cells communicate and function. With many hundreds of members, G protein-coupled receptors are the largest family of signaling receptors throughout the body.

Once a cell's G protein-coupled receptor binds with a natural ligand or a drug, intracellular G proteins and beta arrestins independently mediate various signals. Immediately following, beta arrestins block further signaling of G proteins and recruit proteins to remove the receptor to halt cell signaling. Those receptors can subsequently recycle to the cell surface or be destroyed.

"Receptor down regulation caused by beta arrestins can interfere with drug efficacy because the G protein-coupled receptor that the drug has been targeting is absent from the cell surface," said Carlos E. Alvarez, PhD, principal investigator in the Center for Molecular and Human Genetics at The Research Institute at Nationwide Children's Hospital and lead study author. "This is why patients who are prescribed long-term medication can become drug-tolerant and require higher and higher doses."

In some cases, a drug's ability to trigger beta arrestin effects and block G protein signaling is preferential. Take beta blockers, for example. As the name suggests, beta blockers interfere with the binding to the receptor for epinephrine and other stress hormones, weakening the hormones' effects and therefore being useful in treating irregular heartbeats, prevention of second heart attacks, hypertension and other conditions. Screening has revealed that the beta blocker Carvedilol may be the most ideal for treatment of heart conditions as it reduces the cardiotoxic effects of G protein signaling, while increasing the cardioprotective effects of beta arrestin signaling.

Yet, it seems that beta arrestins may only be part of the cell signaling story. In 2008, Dr. Alvarez discovered a subfamily of arrestins that his team named alpha arrestins. In the current study, Fortune Shea in Dr. Alvarez's lab used biochemical and imaging approaches to further identify the role alpha arrestins play in cell signaling.

He found that alpha arrestins respond to receptor binding and recruit enzymes that chemically modify the receptor to initiate aspects of down regulation. These effects occur in the first five minutes after the receptor is bound, the same time frame that beta arrestins are known to have roles in triggering down regulation. The team is also the first to find 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," says Dr. Alvarez. "It seems that like beta arrestins, alpha arrestins could have great pharmacological relevance."

A major effort in pharmacology is to develop drugs with functional selectivity that either target G protein or beta arrestin signaling effects. Dr. Alvarez foresees alpha arrestins becoming a big player in the refining of 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," he says. "I believe that targeting alpha arrestins will allow us to develop compounds that are more effective and have reduced side effects," says Dr. Alvarez.


'/>"/>

Contact: Erin Pope
Erin.Pope@NationwideChildrens.org
614-355-0495
Nationwide Children's Hospital
Source:Eurekalert

Related medicine news :

1. Targeted Prostate Cancer Biopsies Might Improve Care: Study
2. ADHD Can Cause Lifelong Problems, Study Finds
3. Study of text messaging service shows participants prepared for motherhood
4. In vitro study finds digested formula, but not breast milk, is toxic to cells
5. New Blood Thinner May Help Prevent Leg Clots, Study Finds
6. Minimal Exercise Protects Senior’s Hearts According to Recent Study Reviewed By Projects for Natural Health Choices Inc.
7. Study finds association between oxygen deprivation before birth and ADHD
8. Brain study shows why some people are more in tune with what they want
9. VABC Responds to Study on Use of Cholesterol Lowering Drug Statins on Cancer Patients
10. Transvaginal Mesh Lawsuit Update: New Study Concerning Use of Vaginal Mesh in Prolapse Procedures, Bernstein Liebhard LLP Reports
11. Too Little Sleep Spurs Appetite-Boosting Hormones: Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/25/2017)... Kennett Square, PA (PRWEB) , ... March 25, 2017 , ... ... one priority as a public relations partner. , All through the year, Garden ... stories and press releases, working with key influencers and pitching client’s key messages ...
(Date:3/24/2017)... , ... March 24, 2017 , ... ... which will spark a conversation on the current obstacles facing infection prevention and ... completely preventable deaths caused by these infections. , The print component of ...
(Date:3/24/2017)... ... , ... According to a new study by NCPA Senior Fellow John R. ... rules Congress has directed the CBO to follow. The CBO itself previously recognized Obamacare ... it estimates a reduction in employer-based coverage due to the GOP reform, which is ...
(Date:3/24/2017)... ... March 24, 2017 , ... ... Arizona’s Premier Center for Shamanic Healing and Spiritual Awakening, proudly presents her ... 9--24, 2017. This sacred and spiritual journey during the Summer Solstice will ...
(Date:3/24/2017)... ... March 24, 2017 , ... ... the Advanced ERISA Benefit Claims Litigation seminar in Chicago, Illinois. She will ... The majority of cases litigated under ERISA involve claims for long-term disability benefits. ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... Research and Markets has announced the addition ... - 2035" report to their offering. ... The Deep Learning: Drug Discovery and Diagnostics ... the growing market of deep learning solutions within the healthcare domain. ... emerged as a novel solution to generate relevant insights from medical ...
(Date:3/24/2017)... -- Research and Markets has announced the addition of ... report to their offering. ... The report provides separate comprehensive analytics for the US, Canada ... Asia-Pacific , Latin America , and ... 2015 through 2022. Also, a six-year historic analysis is provided for these ...
(Date:3/24/2017)... March 23, 2017  Mirabilis Medical, a ... technology for non-invasive surgery, announced today CE Mark ... treatment of uterine fibroids throughout the European Union.  ... approval from the US Food and Drug Administration ... System in the United States.  The Mirabilis System ...
Breaking Medicine Technology: