title: Menthol Modulates Pacemaker Potentials through TRPA1 Channels in Cultured Interstitial Cells of Cajal from Murine Small Intestine.
abstract: OBJECTIVE
  ICCs are the pacemaker cells responsible for slow waves in gastrointestinal (GI) smooth muscle, and generate periodic pacemaker potentials in current-clamp mode.
  
  
  METHODS
  The effects of menthol on the pacemaker potentials of cultured interstitial cells of Cajal (ICCs) from mouse small intestine were studied using the whole cell patch clamp technique.
  
  
  RESULTS
  Menthol (1 - 10 μM) was found to induce membrane potential depolarization in a concentration-dependent manner. The effects of various TRP channel antagonists were examined to investigate the receptors involved. The addition of the TRPM8 antagonist, AMTB, did not block menthol-induced membrane potential depolarizations, but TRPA1 antagonists (A967079 or HC-030031) blocked the effects of menthol, as did intracellular GDPβS. Furthermore, external and internal Ca2+ levels were found to depolarize menthol-induced membrane potentials, whereas external Na+ was not. Y-27632 (a Rho kinase inhibitor), SC-560 (a selective COX 1 inhibitor), NS-398 (a selective COX 2 inhibitor), ozagrel (a thromboxane A2 synthase inhibitor) and SQ-29548 (highly selective thromboxane receptor antagonist) were used to investigate the involvements of Rho-kinase, cyclooxygenase (COX), and the thromboxane pathway in menthol-induced membrane potential depolarizations, and all inhibitors were found to block the effect of menthol.
  
  
  CONCLUSIONS
  These results suggest that menthol-induced membrane potential depolarizations occur in a G-protein-, Ca2+-, Rho-kinase-, COX-, and thromboxane A2-dependent manner via TRPA1 receptor in cultured ICCs in murine small intestine. The study shows ICCs are targeted by menthol and that this interaction can affect intestinal motility.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wie
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Myeong Ho
authors.initials: MH
authors.lastname: Jung
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated; D005769:Gastrointestinal Motility / Q000187:drug effects; D006834:Hydrazines / Q000494:pharmacology; D056885:Interstitial Cells of Cajal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology; D008564:Membrane Potentials / Q000187:drug effects*; D008610:Menthol / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010091:Oximes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011687:Purines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D000074025:TRPA1 Cation Channel; D013931:Thromboxanes / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C552888:2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; C560402:A 967079; D000083:Acetanilides; D000577:Amides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010091:Oximes; D011687:Purines; D011720:Pyrazoles; D011725:Pyridines; C115461:SC 560; D000074025:TRPA1 Cation Channel; D013931:Thromboxanes; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C108830:Y 27632; D008610:Menthol; C045749:SQ 29548; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D054460:rho-Associated Kinases; D002118:Calcium