title: A neuroactive steroid inhibits guinea pig airway sensory nerves via Maxi-K channel activation.
abstract: BACKGROUND
  Although neurogenic inflammation via the activation of C-fibers in the airway may have an important role in the pathogenesis of asthma, their regulatory mechanism remains uncertain.
  
  
  OBJECTIVE
  The pharmacological profiles of a neuroactive steroid, allotetrahydrocorticosterone, on the activation of C-fibers in airway tissues were investigated, and the mechanism how a neuroactive steroid regulates airway inflammatory reactions was clarified.
  
  
  METHODS
  The effects of allotetrahydrocorticosterone on electrical field stimulation-induced bronchial smooth muscle contraction in guinea pig airway tissues were investigated. The influences of K+ channel blockers and intracellular protein inhibitors on the effects of allotetrahydrocorticosterone were examined.
  
  
  RESULTS
  Allotetrahydrocorticosterone dose-dependently inhibited electrical field stimulation-induced guinea pig bronchial smooth muscle contraction. The inhibitory effects of allotetrahydrocorticosterone on electrical field stimulation-induced bronchial contraction were reduced by the pretreatment of Maxi-K+ channel blockers, iberiotoxin and charybdotoxin, but not other K+ channel blockers, dendrotoxin or glibenclamide. Pretreatment with pertussis toxin diminished the inhibitory effect of allotetrahydrocorticosterone, but not an adenylate cyclase inhibitor, SQ 22536, nor a specific inhibitor of mitogen-activated protein kinase kinase, PD 98059.
  
  
  CONCLUSIONS
  These findings suggest that allotetrahydrocorticosterone negatively modulates the activation of C-fibers in guinea pig airway tissues via the opening of Maxi-K+ channels and a pertussis toxin-sensitive G-protein-coupled mechanism.
authors.affiliation: Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan. shigemi@dokkyomed.ac.jp
authors.forename: Shigemi
authors.initials: S
authors.lastname: Yoshihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohori
authors.forename: Yumi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Toshio
authors.initials: T
authors.lastname: Abe
authors.forename: Osamu
authors.initials: O
authors.lastname: Arisaka
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D003345:Corticosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; C003676:tetrahydrocorticosterone; D019204:GTP-Binding Proteins; D003345:Corticosterone