title: c-Jun NH₂-terminal kinase contributes to dexmedetomidine-induced contraction in isolated rat aortic smooth muscle.
abstract: OBJECTIVE
  Dexmedetomidine, a full agonist of α2B-adrenoceptors, is used for analgesia and sedation in the intensive care units. Dexmedetomidine produces an initial transient hypertension due to the activation of post-junctional α2B-adrenoceptors on vascular smooth muscle cells (SMCs). The aims of this in vitro study were to identify mitogen-activated protein kinase (MAPK) isoforms that are primarily involved in full, α2B-adrenoceptor agonist, dexmedetomidine-induced contraction of isolated rat aortic SMCs.
  
  
  METHODS
  Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dexmedetomidine (10⁻⁹ to 10⁻⁶ M) dose-response curves were generated in the presence or absence of extracellular signal-regulated kinase (ERK) inhibitor PD 98059, p38 MAPK inhibitor SB 203580, c-Jun NH₂-terminal kinase (JNK) inhibitor SP 600125, L-type calcium channel blocker (verapamil and nifedipine), and α₂-adrenoceptor inhibitor atipamezole. Dexmedetomidine-induced phosphorylation of ERK, JNK, and p38 MAPK in rat aortic SMCs was detected using Western blotting.
  
  
  RESULTS
  SP 600125 (10⁻⁶ to 10⁻⁵ M) attenuated dexmedetomidine-evoked contraction in a concentration- dependent manner, whereas PD 98059 had no effect on dexmedetomidine- induced contraction. SB 203580 (10⁻⁵ M) attenuated dexmedetomidine-induced contraction. Dexmedetomidine-evoked contractions were both abolished by atipamezole and attenuated by verapamil and nifedipine. Dexmedetomidine induced phosphorylation of JNK and p38 MAPK in rat aortic SMCs, but did not induce phosphorylation of ERK.
  
  
  CONCLUSIONS
  Dexmedetomidine-induced contraction involves a JNK- and p38 MAPK-mediated pathway downstream of α₂-adrenoceptor stimulation in rat aortic SMCs. In addition, dexmedetomidine-induced contractions are primarily dependent on calcium influx via L-type calcium channels.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, Jinju 660-702, Korea.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Ok
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Jeong
authors.forename: Jae-Gak
authors.initials: JG
authors.lastname: Kim
authors.forename: Seung-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Hui-Jin
authors.initials: HJ
authors.lastname: Sung
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Seong-Chun
authors.initials: SC
authors.lastname: Kwon
authors.forename: Ju-Tae
authors.initials: JT
authors.lastname: Sohn
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D020927:Dexmedetomidine / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D020033:Protein Isoforms; D011725:Pyridines; C432165:pyrazolanthrone; D020927:Dexmedetomidine; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one