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Federation of American Societies for Experimental Biology
Erscheinungsjahr
2011
Link zum Volltext
Quelle
Wiley Online Library Journals Frontfile Complete
Beschreibungen/Notizen
Coordination of vascular smooth muscle cell (VSMC) constriction in resistance arteries is key to the maintenance of vessel tone and response to stimuli. Pannexins (Panx) are nucleotide‐release channels that are permeable to the vasoconstrictor ATP and thus may play a role in vascular intercellular communication. We investigated the role of Panx in α1‐adrenoreceptor mediated vasoconstriction in thoracodorsal resistance arteries (TDA). Among the three pannexin isoforms, only Panx1 was found to be present in the VSMC of TDA. Functionally, the contractile response of TDA to phenylephrine (PE) was significantly decreased by multiple pannexin inhibitors (mefloquine, probenecid and 10Panx1), a nucleotidase (apyrase) and purinergic receptor inhibitors (suramin and reactive‐blue‐2). We next electroporated TDA with Panx1‐GFP or Panx1 siRNA. Overexpression or underexpression of Panx1 showed enhanced and decreased constriction respectively in response to PE. Lastly, we tested the pannexin inhibitors on KCl responses and demonstrated that none of them altered normal KCl constriction. This result correlated with our co‐immunoprecipitation from TDA, which showed a strong interaction between Panx1 and α1‐adrenoreceptor. In conclusion, our data demonstrates for the first time a potentially key role for Panx1 in the constriction of resistance arteries.