title: Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction.
abstract: BACKGROUND
  The coordination of vascular smooth muscle cell constriction plays an important role in vascular function, such as regulation of blood pressure; however, the mechanism responsible for vascular smooth muscle cell communication is not clear in the resistance vasculature. Pannexins (Panx) are purine-releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of vascular smooth muscle cell constriction.
  
  
  OBJECTIVE
  We investigated the role of pannexins in phenylephrine- and KCl-mediated constriction of resistance arteries.
  
  
  RESULTS
  Western blot, immunohistochemistry, and immunogold labeling coupled to scanning and transmission electron microscopy revealed the presence of Panx1 but not Panx2 or Panx3 in thoracodorsal resistance arteries. Functionally, the contractile response of pressurized thoracodorsal resistance arteries to phenylephrine was decreased significantly by multiple Panx inhibitors (mefloquine, probenecid, and (10)Panx1), ectonucleotidase (apyrase), and purinergic receptor inhibitors (suramin and reactive blue-2). Electroporation of thoracodorsal resistance arteries with either Panx1-green fluorescent protein or Panx1 small interfering RNA showed enhanced and decreased constriction, respectively, in response to phenylephrine. Lastly, the Panx inhibitors did not alter constriction in response to KCl. This result is consistent with coimmunoprecipitation experiments from thoracodorsal resistance arteries, which suggested an association between Panx1 and α1D-adrenergic receptor.
  
  
  CONCLUSIONS
  Our data demonstrate for the first time a key role for Panx1 in resistance arteries by contributing to the coordination of vascular smooth muscle cell constriction and possibly to the regulation of blood pressure.
authors.affiliation: Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Billaud
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Lohman
authors.forename: Adam C
authors.initials: AC
authors.lastname: Straub
authors.forename: Robin
authors.initials: R
authors.lastname: Looft-Wilson
authors.forename: Scott R
authors.initials: SR
authors.lastname: Johnstone
authors.forename: Christina A
authors.initials: CA
authors.lastname: Araj
authors.forename: Angela K
authors.initials: AK
authors.lastname: Best
authors.forename: Faraaz B
authors.initials: FB
authors.lastname: Chekeni
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
authors.forename: Silvia
authors.initials: S
authors.lastname: Penuela
authors.forename: Dale W
authors.initials: DW
authors.lastname: Laird
authors.forename: Brant E
authors.initials: BE
authors.lastname: Isakson
mesh_terms: D000818:Animals; D017630:Connexins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: C547714:Adra1a protein, mouse; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D011189:Potassium Chloride