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JCI online early table of contents: April 6, 2009
Date:4/6/2009

EDITOR'S PICK: Separating the beneficial effects of a drug from the adverse side effects

Nicotinic acid is one of the most effective drugs for raising levels of "good" cholesterol and lowering levels of "bad" cholesterol and other lipids (fats), thereby reducing the risk of heart attack. However, patients often stop taking the drug due to one specific side effect, flushing of the skin that often includes an intense burning and itching sensation. A way to separate the beneficial effects of nicotinic acid from the flushing response has now been elucidated in mice by Robert Lefkowitz and colleagues, at Duke University Medical Center, Durham.

In the study, analysis of human cell lines determined a signaling pathway by which nicotinic acid could initiate the flushing response. This pathway involved the recruitment of beta-arrestin proteins to the GPR109A receptor to which nicotinic acid binds. Interestingly, mice lacking beta-arrestin1 showed a decreased flushing response when treated with nicotinic acid, but the drug retained its beneficial effects on the levels of lipids in the blood. The authors therefore suggest that designing a drug that binds GPR109A but does not stimulate the recruitment of beta-arrestin1 might result in a therapeutic that has beneficial effects on lipid levels without the side effect of flushing.

TITLE: Beta-Arrestin1 mediates nicotinic acidinduced flushing, but not its antilipolytic effect, in mice

AUTHOR CONTACT:
Robert J. Lefkowitz
Duke University Medical Center, Durham, North Carolina, USA.
Phone: (919) 684-3755; Fax: (919) 684-8875; E-mail: lefko001@receptor-biol.duke.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36806


ONCOLOGY: Harnessing immune cells to target skin cancer

One subset of immune c
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Contact: Karen Honey
press_releases@the-jci.org
215-573-1850
Journal of Clinical Investigation
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