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Alterations of the Purinergic Regulation in Mesenteric Arteries of Pannexin-1-Knockout Mice

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

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 effects on smooth muscle contraction are not evident 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 ATP secreted in a Panx1-independent way. Experiments were performed on small mesenteric arteries obtained from Panx1-knockout (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 μM) potentiated the responses to phenylephrine in Panx1+/+ but not in Panx1–/–, while ARL67156 did not affect the contractile responses to the thromboxane A2 receptor agonist in any of the two groups. Contractile responses to exogenous ATP (10 μM) were smaller in Panx1+/+ than in Panx1–/– mice. By contrast, NTPDase1 mRNA content was higher in Panx1+/+ than in Panx1–/– mice. 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 an increased arterial ATP sensitivity and diminished NTPDase1 activity may augment the contractile effects of Panx1-independent ATP.

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References

  1. Panchin Y., Kelmanson I., Matz M., Lukyanov K., Usman N., Lukyanov S. 2000. A ubiquitous family of putative gap junction molecules. Curr. Biol. 10, R473–R474.

  2. Sahu G., Sukumaran S., Bera A.K. 2014. Pannexins form gap junctions with electrophysiological and pharmacological properties distinct from connexins. Sci. Rep. 4, 4955.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Ma W., Compan V., Zheng W., Martin E., North R.A., Verkhratsky A., Surprenant A. 2012. Pannexin 1 forms an anion-selective channel. Pfluegers Arch. 463, 585–592.

    Article  CAS  Google Scholar 

  4. Bao L., Locovei S., Dahl G. 2004. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 572, 65–68.

    Article  PubMed  CAS  Google Scholar 

  5. Shestopalov V.I., Panchin Y. 2008. Pannexins and gap junction protein diversity. Cell. Mol. Life Sci. 65, 376–394.

    Article  PubMed  CAS  Google Scholar 

  6. Penuela S., Gehi R., Laird D.W. 2013. The biochemistry and function of pannexin channels. Biochim. Biophys. Acta 1828, 15–22.

    Article  PubMed  CAS  Google Scholar 

  7. Lazarowski E.R. 2012. Vesicular and conductive mechanisms of nucleotide release. Purinergic Signal. 8, 359–373.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Lohman A.W., Billaud M., Isakson B.E. 2012. Mechanisms of ATP release and signalling in the blood vessel wall. Cardiovasc. Res. 95, 269–280.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Burnstock G. 2017. Purinergic signaling in the cardiovascular system. Circ. Res. 120, 207–228.

    Article  PubMed  CAS  Google Scholar 

  10. Ralevic V., Dunn W.R. 2015. Purinergic transmission in blood vessels. Auton. Neurosci. 191, 48–66.

    Article  PubMed  CAS  Google Scholar 

  11. Lohman A.W., Billaud M., Straub A.C., Johnstone S.R., Best A.K., Lee M., Barr K., Penuela S., Laird D.W., Isakson B.E. 2012. Expression of pannexin isoforms in the systemic murine arterial network. J. Vasc. Res. 49, 405–416.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Gaynullina D., Shestopalov V.I., Panchin Y., Tarasova O.S. 2015. Pannexin 1 facilitates arterial relaxation via an endothelium-derived hyperpolarization mechanism. FEBS Lett. 589, 1164–1170.

    Article  PubMed  CAS  Google Scholar 

  13. Gaynullina D., Tarasova O.S., Kiryukhina O.O., Shestopalov V.I., Panchin Y. 2014. Endothelial function is impaired in conduit arteries of pannexin1 knockout mice. Biol. Direct. 9, 8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Billaud M., Lohman A.W., Straub A.C., Looft-Wilson R., Johnstone S.R., Araj C.A., Best A.K., Chekeni F.B., Ravichandran K.S., Penuela S., Laird D.W., Isakson B.E. 2011. Pannexin1 regulates α1-adrenergic receptormediated vasoconstriction. Circ. Res. 109, 80–85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Billaud M., Chiu Y.-H., Lohman A.W., Parpaite T., Butcher J.T., Mutchler S.M., DeLalio L.J., Artamonov M.V., Sandilos J.K., Best A.K., Somlyo A.V., Thompson R.J., Le T.H., Ravichandran K.S., Bayliss D.A., Isakson B.E. 2015. A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells. Sci. Signal. 8, ra17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Angus J.A., Betrie A.H., Wright C.E. 2015. Pannexin-1 channels do not regulate α1-adrenoceptor-mediated vasoconstriction in resistance arteries. Eur. J. Pharmacol. 750C, 43–51.

    Article  CAS  Google Scholar 

  17. Angus J.A., Wright C.E. 2015. ATP is not involved in α1-adrenoceptor-mediated vasoconstriction in resistance arteries. Eur. J. Pharmacol. 769, 162–166.

  18. Methven L., Simpson P., McGrath J. 2009. Alpha1A/B-knockout mice explain the native alpha1D-adrenoceptor’s role in vasoconstriction and show that its location is independent of the other α1-subtypes. Br. J. Pharmacol. 158, 1663–1675.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Vial C., Evans R.J. 2002. P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. Mol. Pharmacol. 62, 1438–1445.

    Article  PubMed  CAS  Google Scholar 

  20. Angus J., Wright C. 2016. Novel α1-adrenoceptor antagonism by the fluoroquinolone antibiotic trovafloxacin. Eu. J. Pharmacol. 791, 179–184.

    Article  CAS  Google Scholar 

  21. Dvoriantchikova G., Ivanov D., Barakat D., Grinberg A., Wen R., Slepak V.Z., Shestopalov V.I. 2012. Genetic ablation of Pannexin1 protects retinal neurons from ischemic injury. PLoS One. 7, e31991.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Mulvany M.J., Halpern W. 1977. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ. Res. 41, 19–26.

    Article  PubMed  CAS  Google Scholar 

  23. Kauffenstein G., Drouin A., Thorin-Trescases N., Bachelard H., Robaye B., D’Orléans-Juste P., Marceau F., Thorin E., Sévigny J. 2010. NTPDase1 (CD39) controls nucleotide-dependent vasoconstriction in mouse. Cardiovasc. Res. 85, 204–213.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Kauffenstein G., Fürstenau C.R., D’Orléans-Juste P., Sévigny J. 2010. The ecto-nucleotidase NTPDase1 differentially regulates P2Y1 and P2Y2 receptor-dependent vasorelaxation. Br. J. Pharmacol. 159, 576–585.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Robson S.C., Wu Y., Sun X., Knosalla C., Dwyer K., Enjyoji K. 2005. Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in transplantation. Semin. Thromb. Hemost. 31, 217–233.

    Article  PubMed  CAS  Google Scholar 

  26. Teng B., Fil D., Tilley S.L., Ledent C., Krahn T., Mustafa S.J. 2013. Functional and RNA expression profile of adenosine receptor subtypes in mouse mesenteric arteries. J. Cardiovasc. Pharmacol. 61, 70–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Koltsova S.V., Maximov G.V., Kotelevtsev S.V., Lavoie J.L., Tremblay J., Grygorczyk R., Hamet P., Orlov S.N. 2009. Myogenic tone in mouse mesenteric arteries: Evidence for P2Y receptor-mediated, Na+, K+ 2Cl–cotransport-dependent signaling. Purinergic Signal. 5, 343–349.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Lévesque S.A., Lavoie É.G., Lecka J., Bigonnesse F., Sévigny J. 2007. Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases. Br. J. Pharmacol. 152, 141–150.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Villa-Bellosta R., Wang X., Millan J.L., Dubyak G.R., O’Neill W.C. 2011. Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle. Am. J. Physiol. 301, H61–H68.

    CAS  Google Scholar 

  30. Bao R., Shui X., Hou J., Li J., Deng X., Zhu X., Yang T. 2016. Adenosine and the adenosine A2A receptor agonist, CGS21680, upregulate CD39 and CD73 expression through E2F-1 and CREB in regulatory T cells isolated from septic mice. Int. J. Mol. Med. 38, 969–975.

    Article  PubMed  CAS  Google Scholar 

  31. Westfall T.D., Kennedy C., Sneddon P. 1996. Enhancement of sympathetic purinergic neurotransmission in the guinea-pig isolated vas deferens by the novel ecto-ATPase inhibitor ARL 67156. Br. J. Pharmacol. 117, 867–872.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Long J.B., Segal S.S. 2009. Quantifying perivascular sympathetic innervation: Regional differences in male C57BL/6 mice at 3 and 20 months. J. Neurosci. Methods. 184, 124–128.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Takahashi-Sato K., Murakawa M., Kimura J., Ito M., Matsuoka I. 2013. Loss of ectonucleotidases from the coronary vascular bed after ischemia–reperfusion in isolated rat heart. BMC Cardiovasc. Disord. 13, 53.

    CAS  Google Scholar 

  34. Crikis S., Lu B., Murray-Segal L. M., Selan C., Robson S.C., D’Apice A.J.F., Nandurkar H.H., Cowan P.J., Dwyer K.M. 2010. Transgenic overexpression of CD39 protects against renal ischemia–reperfusion and transplant vascular injury. Am. J. Transplant. 10, 2586–2595.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Souza C.G., de Böhmer A.E., Müller A.P., Oses J.P., Viola G.G., Lesczinski D.N., Souza D.G. de Knorr L., Moreira J.D., Lhullier F., Souza D.O., Perry M.L.S. 2010. Effects of a highly palatable diet on lipid and glucose parameters, nitric oxide, and ectonucleotidases activity. Appl. Physiol. Nutr. Metab. 35, 591–597.

    Article  PubMed  CAS  Google Scholar 

  36. Bergamin L.S., Braganhol E., Zanin R.F., Edelweiss M.I.A., Battastini A.M.O. 2012. Ectonucleotidases in tumor cells and tumor-associated immune cells: An overview. J. Biomed. Biotechnol. 2012, 959848.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Correspondence to O. S. Tarasova.

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Original Russian Text © O.O. Kiryukhina, D.K. Gaynullina, Y.V. Panchin, V.I. Shestopalov, O.S. Tarasova, 2017, published in Biologicheskie Membrany, 2017, Vol. 34, No. 6, pp. 137–146.

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Kiryukhina, O.O., Gaynullina, D.K., Panchin, Y.V. et al. Alterations of the Purinergic Regulation in Mesenteric Arteries of Pannexin-1-Knockout Mice. Biochem. Moscow Suppl. Ser. A 12, 62–69 (2018). https://doi.org/10.1134/S1990747818010075

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