Alterations of the purinergic regulation in mesenteric arteries of pannexin-1-knockout miceстатья
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Аннотация:Pannexin 1 (Panx1) forms plasma membrane channels that release ATP, an important vascular tone regulator. However, despite the abundant expression of Panx1 in the vascular system, its effect on smooth muscle contraction does not appear in all arteries. In this study, we tested the hypothesis that the functional consequences of Panx1 deficiency can be masked by the augmented action of Panx1-independent ATP. The experiments were performed on small mesenteric arteries obtained from Panx1 knockout mice (Panx1-/-) and C57Bl/6 (Panx1+/+) male mice using wire myography of endothelium-denuded arterial preparations and reverse-transcription quantitative PCR techniques. Arterial contractile responses to phenylephrine did not differ in two experimental groups. Ecto-ATPase inhibitor ARL67156 (100 microM) potentiated the responses to phenylephrine in Panx1+/+ but not Panx1-/-, while ARL67156 did not affected the contractile responses to the thromboxane A2 receptor agonist in any of the two groups. Contractile responses to exogenous ATP (10 microM) were smaller in Panx1+/+ compared to Panx1-/-. By contrast, NTPDase1 mRNA content were higher in Panx1+/+ than in Panx1-/-. These results suggest that ATP released from smooth muscle cells through Panx1 channels can potentiate contractile responses of murine mesenteric arteries upon activation of α1-adrenoceptors. In Panx1-/- mice the increased arterial ATP-sensitivity and diminished NTPDase1 activity may augment the contractile effects of Panx1-independent ATP.