S-nitrosothiols: Possibilities in Fighting Asthma and Heart Disease

Jonathan S. Stamler, M.D.
Howard Hughes Medical Institute and Duke University Medical Center
U19ES012496

Jonathan Stamler and colleagues at Duke University and the Howard Hughes Medical Institute report in the May 4th issue of Cell new findings suggesting the endogenous compound S-nitrosothiol may have clinical implications for a variety of diseases including asthma and heart failure. They found that S-nitrosothiol, a specialized form of nitric oxide, inhibits a key regulatory system that ordinarily shuts off receptors once they have been stimulated.

The G-protein coupled receptors represent the largest known family of cell-surface receptors and are involved in many aspects of mammalian physiology including processes as diverse as responses to odorants, light, and pain. About half of all drugs on the market today target the G-protein coupled receptors. Many of these drugs lose their effectiveness over time because the receptors they target are recycled into the cell and are turned off.

In a series of experiments in laboratory animals and cell culture systems, the researchers found that a lack of nitric oxide led to a decrease in the number of beta adrenergic receptors on the surface of cells. Administration of S-nitrosothiols to mice prevented the receptors from being turned off. If these findings are confirmed in humans, they may lead to the development of new non-sensitizing therapeutic agents for many conditions such as heart disease, asthma, high blood pressure, chronic pain, diabetes, and others.

Citation: Whalen EJ, Foster MW, Matsumoto A, Ozawa K, Violin JD, Que LG, Nelson CD, Benhar M, Keys JR, Rockman HA, Koch WJ, Daaka Y, Lefkowitz RJ, Stamler JS. Regulation of beta-adrenergic receptor signaling by S-nitrosylation of G-protein-coupled receptor kinase 2. Cell. 2007 May 4;129(3):511-22.