Deglycosylated Azithromycin Targets Transgelin to Enhance Intestinal Smooth Muscle Function

Azithromycin (AZM) has been widely used as an antibacterial drug for many years. It has also been used to treat delayed gastric emptying. However, it exerts several side effects. We found that deglycosylated AZM (Deg-AZM or CP0119), an AZM metabolite, is a positively strong intestinal agonist that may result in the intestinal mobility experienced by patients after AZM administration. We confirmed that Deg-AZM can function strongly on intestinal peristalsis and identified transgelin as its potential molecular target. Furthermore, our pharmacological studies showed that the binding of Deg-AZM to transgelin enhanced the contractility of intestinal smooth muscle cells by facilitating the assembly of actin filaments into tight bundles and stress fibers. Specifically, Deg-AZM promoted intestinal peristaltic activity in wild-type mice but not in transgelin (−/−) mice. Moreover, Deg-AZM did not exert antibacterial activity and did not disrupt intestinal flora. Thus, Deg-AZM may become a potential drug for slow-transit constipation treatment.