title: GPR39 is coupled to TMEM16A in intestinal fibroblast-like cells.
abstract: 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, Zn(2+), induced large currents and membrane depolarization in FLCs cultured from wild-type mice, but not Gpr39(-/-) mice. This Zn(2+)-induced current could be suppressed by application of a TMEM16A antagonist, CaCC(inh)-A01, or by silencing Tmem16a expression. These data suggest that GPR39 might modulate gut motility via regulating TMEM16A function in FLCs.
authors.affiliation: Gastrointestinal Disease Area, Novartis Horsham Research Centre, Horsham, United Kingdom. fanning.zeng@novartis.com
authors.forename: Fanning
authors.initials: F
authors.lastname: Zeng
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wind
authors.forename: Conor
authors.initials: C
authors.lastname: McClenaghan
authors.forename: J Martin
authors.initials: JM
authors.lastname: Verkuyl
authors.forename: Robert P
authors.initials: RP
authors.lastname: Watson
authors.forename: Mark S
authors.initials: MS
authors.lastname: Nash
mesh_terms: D000818:Animals; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D005347:Fibroblasts / Q000166:cytology*; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000166:cytology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D007150:Immunohistochemistry / Q000379:methods; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009474:Neurons; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry
chemical_list: C531181:ANO1 protein, mouse; D000075369:Anoctamin-1; D018118:Chloride Channels; C512928:GPR39 protein, mouse; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D015032:Zinc