GPR39 Is Coupled to TMEM16A in Intestinal Fibroblast-Like Cells

GPR39 is a GPCR implicated as a regulator of gastrointestinal motility, although the mechanism remains elusive. Here, we report that GPR39 is expressed by a specific cell population cultured from mouse small intestine muscle layers, which was subsequently identified as fibroblast-like cells (FLCs) that have recently been shown to modulate gut motility. Application of the GPR39 agonist, Zn2+, induced large currents and membrane depolarization in FLCs cultured from wild-type mice, but not Gpr39−/− mice. This Zn2+-induced current could be suppressed by application of a TMEM16A antagonist, CaCCinh-A01, or by silencing Tmem16a expression. These data suggest that GPR39 might modulate gut motility via regulating TMEM16A function in FLCs.