Document Detail


Pannexin1 regulates α1-adrenergic receptor- mediated vasoconstriction.
MedLine Citation:
PMID:  21546608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RATIONALE: 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.
METHODS AND 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:
Marie Billaud; Alexander W Lohman; Adam C Straub; Robin Looft-Wilson; Scott R Johnstone; Christina A Araj; Angela K Best; Faraaz B Chekeni; Kodi S Ravichandran; Silvia Penuela; Dale W Laird; Brant E Isakson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-05
Journal Detail:
Title:  Circulation research     Volume:  109     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-24     Completed Date:  2011-08-22     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  80-5     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Connexins / analysis,  physiology*
Mice
Muscle, Smooth, Vascular / chemistry,  cytology,  physiology
Myocytes, Smooth Muscle / chemistry
Nerve Tissue Proteins / analysis,  physiology*
Phenylephrine / pharmacology
Potassium Chloride / pharmacology
Receptors, Adrenergic, alpha-1 / physiology*
Vascular Resistance
Vasoconstriction / drug effects,  physiology*
Grant Support
ID/Acronym/Agency:
HL088554/HL/NHLBI NIH HHS; R01 HL088554/HL/NHLBI NIH HHS; R01 HL088554-05/HL/NHLBI NIH HHS; R15 HL102742-01/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Adra1a protein, mouse; 0/Connexins; 0/Nerve Tissue Proteins; 0/Panx1 protein, mouse; 0/Receptors, Adrenergic, alpha-1; 1WS297W6MV/Phenylephrine; 660YQ98I10/Potassium Chloride
Comments/Corrections

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