January 1, 2008

Risky Receptor Regulators

By Roberta Gottlieb, M.D.

Members of the Gottlieb lab and collaborators from the Scripps Research Institute recently published a paper reporting potentially dangerous effects of a drug that binds to a specific receptor for the bioactive lipid sphingosine-1-phosphate (S-1-P). The body uses S-1-P to regulate immune cells, activate platelets, stimulate growth of new blood vessels, and a variety of other processes. The findings of this study revealed that SEW-2871, which selectively activates only type 1 receptors for S-1-P, can trigger cardiac arrhythmias, but only after an episode of ischemia and reperfusion. Although the study was performed with isolated rat hearts, it has clinical relevance because selective S-1-P receptor agonists are in early clinical trials as immune modulators. The findings suggest that some S-1-P receptor agonists may carry unexpected risks in patients with underlying ischemic heart disease.