title: Signalling pathways responsible for the methylisogermabullone-induced contraction of ileal longitudinal muscles.
abstract: OBJECTIVE
  We have previously reported that methylisogermabullone (MIGB) stimulates small bowel motility through activation of acetylcholinergic receptors. This study investigated the cellular signalling pathways implicated in the regulation of ileal contractility by MIGB.
  
  
  METHODS
  The ileal longitudinal muscles prepared from rats were treated with MIGB isolated from radish roots, and muscle contractility and protein expression were measured by force transducer and Western blot, respectively.
  
  
  RESULTS
  MIGB at 30 µm induced a sustained phasic contraction of ileal longitudinal muscles. Acetylcholine (ACh, 0.5 µm) and MIGB stimulated translocation of protein kinase C (PKC) to cell membrane of ileal longitudinal muscles, and these stimulatory effects were remarkably attenuated by atropine (0.5 µm). ACh and MIGB induced phosphorylation of ERK 1/2 and p38 MAPKs in ileal longitudinal muscles, and they also phosphorylated the caldesmon and 20-kDa regulatory light chain of myosin (MLC(20) ). Additionally, PD-98058 (10 µm), a selective ERK 1/2 MAPK inhibitor, and SB-203580 (10 µm), a selective p38 MAPK inhibitor, significantly reduced the MIGB-induced contraction of ileal longitudinal muscles.
  
  
  CONCLUSIONS
  The muscarinic receptor activated by MIGB translocates the PKC to cell membrane which phosphorylates the ERK 1/2 and p38 MAPKs, resulting in subsequent phosphorylation of caldesmon and MLC(20) . These cellular events likely converge on the contraction of ileal longitudinal muscles in rats.
authors.affiliation: Jeonju Biomaterials Institute, College of Medicine, Wonkwang University, Jeonbuk, Korea. wkuniv@wonkwang.ac.kr
authors.forename: Seung Il
authors.initials: SI
authors.lastname: Jeong
authors.forename: Oh Deog
authors.initials: OD
authors.lastname: Kwon
authors.forename: Seung Chun
authors.initials: SC
authors.lastname: Kwon
authors.forename: Kyu Yong
authors.initials: KY
authors.lastname: Jung
mesh_terms: D000475:Alkenes / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D009930:Organic Chemicals / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000475:Alkenes; D000577:Amides; D002148:Calmodulin-Binding Proteins; D007093:Imidazoles; D018994:Myosin Light Chains; D009930:Organic Chemicals; C466090:PD 98058; D011725:Pyridines; D011976:Receptors, Muscarinic; C509209:methylisogermabullone; D001285:Atropine; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580