P2Y2 receptor activation decreases blood pressure via intermediate conductance potassium channels and connexin 37

Acta Physiologica

Volumn 213, Issue 3, 2015, Pages 628-641

  Dominguez Rieg, J A ^a,b   Burt, J M ^c   Ruth, P ^d   Rieg, T ^b,e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^c UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF TÜBINGEN   (Germany)

^e UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

Gap junction; Hyperpolarization; K+ channels; Myogenic tone; P2 receptors; Signalling

Indexed keywords

CONNEXIN 37; CONNEXIN 40; POTASSIUM CHANNEL; POTASSIUM CHANNEL KCA1.1; POTASSIUM CHANNEL KCA3.1; PURINERGIC P2Y2 RECEPTOR; UNCLASSIFIED DRUG; ENDOTHELIAL NITRIC OXIDE SYNTHASE; GAP JUNCTION PROTEIN; INOSINE; INS45973; INTERMEDIATE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL; KCNMA1 PROTEIN, MOUSE; KCNN4 PROTEIN, MOUSE; LARGE CONDUCTANCE CALCIUM ACTIVATED POTASSIUM CHANNEL ALPHA SUBUNIT; NOS3 PROTEIN, MOUSE; PURINERGIC P2Y RECEPTOR AGONIST; URIDINE TRIPHOSPHATE;

ADULT; ANIMAL EXPERIMENT; ARTERIAL PRESSURE; ARTICLE; BLOOD PRESSURE; BLOOD VESSEL REACTIVITY; CONTROLLED STUDY; ENDOTHELIAL DERIVED HYPERPOLARIZATION; HEART RATE; HYPERPOLARIZATION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; VASODILATATION; 129 MOUSE; ANALOGS AND DERIVATIVES; ANIMAL; C57BL MOUSE; DEFICIENCY; DOSE RESPONSE; DRUG EFFECTS; ENDOTHELIUM CELL; GENETICS; KNOCKOUT MOUSE; METABOLISM; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE;

ANIMALS; BLOOD PRESSURE; CONNEXINS; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; HEART RATE; INOSINE; INTERMEDIATE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS; LARGE-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNEL ALPHA SUBUNITS; MALE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; MUSCLE, SMOOTH, VASCULAR; MYOCYTES, SMOOTH MUSCLE; NITRIC OXIDE SYNTHASE TYPE III; PURINERGIC P2Y RECEPTOR AGONISTS; RECEPTORS, PURINERGIC P2Y2; SIGNAL TRANSDUCTION; URIDINE TRIPHOSPHATE; VASODILATION;

EID: 84921449667     PISSN: 17481708     EISSN: 17481716     Source Type: Journal    
DOI: 10.1111/apha.12446     Document Type: Article

References (89)

1. Abbracchio, M.P., Burnstock, G., Boeynaems, J.M., Barnard, E.A., Boyer, J.L., Kennedy, C., Knight, G.E., Fumagalli, M., Gachet, C., Jacobson, K.A. & Weisman, G.A. 2006. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58, 281-341.
2. +]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. J Cardiovasc Pharmacol 21, 423-429.
3. Bar, I., Guns, P.J., Metallo, J., Cammarata, D., Wilkin, F., Boeynams, J.M., Bult, H. & Robaye, B. 2008. Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Mol Pharmacol 74, 777-784.
4. 2+-activated potassium channel Kcnn4. J Biol Chem 279, 47681-47687.
5. Boarder, M.R. & Hourani, S.M.O. 1998. The regulation of vascular function by P2 receptors: multiple sites and multiple receptors. Trends Pharmacol Sci 19, 99-107.
6. Brahler, S., Kaistha, A., Schmidt, V.J., Wolfle, S.E., Busch, C., Kaistha, B.P., Kacik, M., Hasenau, A.L., Grgic, I., Si, H. et al. 2009. Genetic deficit of SK3 and IK1 channels disrupts the endothelium-derived hyperpolarizing factor vasodilator pathway and causes hypertension. Circulation 119, 2323-2332.
7. Burnstock, G. 2009. Purinergic regulation of vascular tone and remodelling. Auton Autacoid Pharmacol 29, 63-72.
8. Buvinic, S., Briones, R. & Huidobro-Toro, J.P. 2002. P2Y(1) and P2Y(2) receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed. Br J Pharmacol 136, 847-856.
9. Chaytor, A.T., Bakker, L.M., Edwards, D.H. & Griffith, T.M. 2005. Connexin-mimetic peptides dissociate electrotonic EDHF-type signalling via myoendothelial and smooth muscle gap junctions in the rabbit iliac artery. Br J Pharmacol 144, 108-114.
10. Crecelius, A.R., Kirby, B.S., Richards, J.C., Garcia, L.J., Voyles, W.F., Larson, D.G., Luckasen, G.J. & Dinenno, F.A. 2011. Mechanisms of ATP-mediated vasodilation in humans: modest role for nitric oxide and vasodilating prostaglandins. Am J Physiol Heart Circ Physiol 301, H1302-H1310.
11. Damkjaer, M., Nielsen, G., Bodendiek, S., Staehr, M., Gramsbergen, J.B., de Wit, C., Jensen, B.L., Simonsen, U., Bie, P., Wulff, H. & Kohler, R. 2012. Pharmacological activation of KCa3.1/KCa2.3 channels produces endothelial hyperpolarization and lowers blood pressure in conscious dogs. Br J Pharmacol 165, 223-234.
12. Dietrich, H.H., Kajita, Y. & Dacey, R.G. 1996. Local and conducted vasomotor responses in isolated rat cerebral arterioles. Am J Physiol Heart Circ Physiol 271, H1109-H1116.
13. Dora, K.A., Sandow, S.L., Gallagher, N.T., Takano, H., Rummery, N.M., Hill, C.E. & Garland, C.J. 2003. Myoendothelial gap junctions may provide the pathway for EDHF in mouse mesenteric artery. J Vasc Res 40, 480-490.
14. Edwards, G., Feletou, M. & Weston, A.H. 2010. Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch 459, 863-879.
15. +-channels suppresses EDHF-mediated vasodilation. Br J Pharmacol 138, 594-601.
16. Fang, J.S., Angelov, S.N., Simon, A.M. & Burt, J.M. 2011. Cx37 deletion enhances vascular growth and facilitates ischemic limb recovery. Am J Physiol Heart Circ Physiol 301, H1872-H1881.
17. Fang, J.S., Angelov, S.N., Simon, A.M. & Burt, J.M. 2012. Cx40 is required for, and cx37 limits, postischemic hindlimb perfusion, survival and recovery. J Vasc Res 49, 2-12.
18. Feletou, M. 2009. Calcium-activated potassium channels and endothelial dysfunction: therapeutic options?. Br J Pharmacol 156, 545-562.
19. Feletou, M. & Vanhoutte, P.M. 2009. EDHF: an update. Clin Sci (Lond) 117, 139-155.
20. Fenton, R.A., Murray, F., Dominguez Rieg, J.A., Tang, T., Levi, M. & Rieg, T. 2014. Renal phosphate wasting in the absence of adenylyl cyclase 6. J Am Soc Nephrol 25, 2822-2834.
21. Figueroa, X.F. & Duling, B.R. 2008. Dissection of two Cx37-independent conducted vasodilator mechanisms by deletion of Cx40: electrotonic versus regenerative conduction. Am J Physiol Heart Circ Physiol 295, H2001-H2007.
22. Figueroa, X.F. & Duling, B.R. 2009. Gap junctions in the control of vascular function. Antioxid Redox Signal 11, 251-266.
23. Figueroa, X.F., Isakson, B.E. & Duling, B.R. 2004. Connexins: gaps in our knowledge of vascular function. Physiology (Bethesda) 19, 277-284.
24. Garland, C.J., Hiley, C.R. & Dora, K.A. 2011. EDHF: spreading the influence of the endothelium. Br J Pharmacol 164, 839-852.
25. + channels in normal and impaired EDHF-dilator responses-relevance to cardiovascular pathologies and drug discovery. Br J Pharmacol 157, 509-526.
26. Griffith, T.M., Chaytor, A.T., Taylor, H.J., Giddings, B.D. & Edwards, D.H. 2002. cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing electrotonic conduction via gap junctions. Proc Natl Acad Sci USA 99, 6392-6397.
27. Guns, P.J., Korda, A., Crauwels, H.M., Van Assche, T., Robaye, B., Boeynaems, J.M. & Bult, H. 2005. Pharmacological characterization of nucleotide P2Y receptors on endothelial cells of the mouse aorta. Br J Pharmacol 146, 288-295.
28. 2-deficient mice. Br J Pharmacol 147, 569-574.
29. Haddock, R.E., Grayson, T.H., Brackenbury, T.D., Meaney, K.R., Neylon, C.B., Sandow, S.L. & Hill, C.E. 2006. Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40. Am J Physiol Heart Circ Physiol 291, H2047-H2056.
30. Hammer, L.W., Overstreet, C.R., Choi, J. & Hester, R.L. 2003. ATP stimulates the release of prostacyclin from perfused veins isolated from the hamster hindlimb. Am J Physiol Regul Integr Comp Physiol 285, R193-R199.
31. Holzmann, S., Kukovetz, W.R., Windischhofer, W., Paschke, E. & Graier, W.F. 1994. Pharmacologic differentiation between endothelium-dependent relaxations sensitive and resistant to nitro-L-arginine in coronary arteries. J Cardiovasc Pharmacol 23, 747-756.
32. Horiuchi, T., Dietrich, H.H., Tsugane, S. & Dacey, R.G. 2001. Analysis of purine- and pyrimidine-induced vascular responses in the isolated rat cerebral arteriole. Am J Physiol Heart Circ Physiol 280, H767-H776.
33. Hrafnkelsdottir, T., Erlinge, D. & Jern, S. 2001. Extracellular nucleotides ATP and UTP induce a marked acute release of tissue-type plasminogen activator in vivo in man. Thromb Haemost 85, 875-881.
34. Inscho, E.W. 2009. ATP, P2 receptors and the renal microcirculation. Purinergic Signal 5, 447-460.
35. Isakson, B.E. & Duling, B.R. 2005. Heterocellular contact at the myoendothelial junction influences gap junction organization. Circ Res 97, 44-51.
36. Janigro, D., Nguyen, T.S., Meno, J., West, G.A. & Winn, H.R. 1997. Endothelium-dependent regulation of cerebrovascular tone by extracellular and intracellular ATP. Am J Physiol Heart Circ Physiol 273, H878-H885.
37. Jobs, A., Schmidt, K., Schmidt, V.J., Lubkemeier, I., van Veen, T.A., Kurtz, A., Willecke, K. & de Wit, C. 2012. Defective Cx40 maintains Cx37 expression but intact Cx40 is crucial for conducted dilations irrespective of hypertension. Hypertension 60, 1422-1429.
38. Kauffenstein, G., Drouin, A., Thorin-Trescases, N., Bachelard, H., Robaye, B., D'Orleans-Juste, P., Marceau, F., Thorin, E. & Sevigny, J. 2010. NTPDase1 (CD39) controls nucleotide-dependent vasoconstriction in mouse. Cardiovasc Res 85, 204-213.
39. Kennedy, C. & Burnstock, G. 1985. ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery. Blood Vessels 22, 145-155.
40. Kennedy, C., Delbro, D. & Burnstock, G. 1985. P2-purinoceptors mediate both vasodilation (via the endothelium) and vasoconstriction of the isolated rat femoral artery. Eur J Pharmacol 107, 161-168.
41. +-channel transgenic mice. Pflugers Arch 459, 969-976.
42. Krattinger, N., Capponi, A., Mazzolai, L., Aubert, J.F., Caille, D., Nicod, P., Waeber, G., Meda, P. & Haefliger, J.A. 2007. Connexin40 regulates renin production and blood pressure. Kidney Int 72, 814-822.
43. von Kugelgen, I. & Starke, K. 1990. Evidence for two separate vasoconstriction-mediating nucleotide receptors, both distinct from the P2x-receptor, in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides. Naunyn Schmiedebergs Arch Pharmacol 341, 538-546.
44. von Kugelgen, I., Haussinger, D. & Starke, K. 1987. Evidence for a vasoconstriction-mediating receptor for UTP, distinct from the P2 purinoceptor, in rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol 336, 556-560.
45. Lohman, A.W. & Isakson, B.E. 2014. Differentiating connexin hemichannels and pannexin channels in cellular ATP release. FEBS Lett 588, 1379-1388.
46. 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.
47. Malmsjo, M., Erlinge, D., Hogestatt, E.D. & Zygmunt, P.M. 1999. Endothelial P2Y receptors induce hyperpolarisation of vascular smooth muscle by release of endothelium-derived hyperpolarising factor. Eur J Pharmacol 364, 169-173.
48. Malmsjo, M., Chu, Z.M., Croft, K., Erlinge, D., Edvinsson, L. & Beilin, L.J. 2002. P2Y receptor-induced EDHF vasodilatation is of primary importance for the regulation of perfusion pressure in the peripheral circulation of the rat. Acta Physiol Scand 174, 301-309.
49. Mather, S., Dora, K.A., Sandow, S.L., Winter, P. & Garland, C.J. 2005. Rapid endothelial cell-selective loading of connexin 40 antibody blocks endothelium-derived hyperpolarizing factor dilation in rat small mesenteric arteries. Circ Res 97, 399-407.
50. McMillan, M.R., Burnstock, G. & Haworth, S.G. 1999. Vasoconstriction of intrapulmonary arteries to P2-receptor nucleotides in normal and pulmonary hypertensive newborn piglets. Br J Pharmacol 128, 549-555.
51. Min, K., Munarriz, R., Yerxa, B.R., Goldstein, I., Shaver, S.R., Cowlen, M.S. & Traish, A.M. 2003. Selective P2Y2 receptor agonists stimulate vaginal moisture in ovariectomized rabbits. Fertil Steril 79, 393-398.
52. Mizumori, M., Ham, M., Guth, P.H., Engel, E., Kaunitz, J.D. & Akiba, Y. 2009. Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum. J Physiol 587, 3651-3663.
53. Persson, P.B. 2013. Good publication practice in physiology 2013: revised author guidelines for Acta Physiologica. Acta Physiol 209, 250-253.
54. 2-receptor tone. FASEB J 24, 2056-2065.
55. Radtke, J., Schmidt, K., Wulff, H., Kohler, R. & de Wit, C. 2013. Activation of KCa3.1 by SKA-31 induces arteriolar dilatation and lowers blood pressure in normo- and hypertensive connexin40-deficient mice. Br J Pharmacol 170, 293-303.
56. Ralevic, V. & Burnstock, G. 1991a. Effects of purines and pyrimidines on the rat mesenteric arterial bed. Circ Res 69, 1583-1590.
57. Ralevic, V. & Burnstock, G. 1991b. Roles of P2-purinoceptors in the cardiovascular system. Circulation 84, 1-14.
58. Ralevic, V. & Burnstock, G. 1996a. Discrimination by PPADS between endothelial P2Y- and P2U-purinoceptors in the rat isolated mesenteric arterial bed. Br J Pharmacol 118, 428-434.
59. Ralevic, V. & Burnstock, G. 1996b. Relative contribution of P2U- and P2Y-purinoceptors to endothelium-dependent vasodilatation in the golden hamster isolated mesenteric arterial bed. Br J Pharmacol 117, 1797-1802.
60. Ralevic, V. & Burnstock, G. 2003. Involvement of purinergic signaling in cardiovascular diseases. Drug News Perspect 16, 133-140.
61. 2 receptors mediate rapid Ca(2+) mobilization, membrane hyperpolarization and nitric oxide production in human vascular endothelial cells. Cell Calcium 49, 240-248.
62. Rayment, S.J., Latif, M.L., Ralevic, V. & Alexander, S.P.H. 2007. Evidence for the Expression of Multiple Uracil Nucleotide-Stimulated P2 Receptors Coupled to Smooth Muscle Contraction in Porcine Isolated Arteries. Br J Pharmacol 150, 604-612.
63. Rieg, T., Richter, K., Osswald, H. & Vallon, V. 2004. Kidney function in mice: thiobutabarbital versus alpha-chloralose anesthesia. Naunyn Schmiedebergs Arch Pharmacol 370, 320-323.
64. Rieg, T., Steigele, H., Schnermann, J., Richter, K., Osswald, H. & Vallon, V. 2005. Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. J Pharmacol Exp Ther 313, 403-409.
65. + and water reabsorption. FASEB J 21, 3717-3726.
66. Rieg, T., Vallon, V., Sausbier, M., Sausbier, U., Kaissling, B., Ruth, P. & Osswald, H. 2007b. The role of the BK channel in potassium homeostasis and flow-induced renal potassium excretion. Kidney Int 72, 566-573.
67. Rieg, T., Gerasimova, M., Boyer, J.L., Insel, P.A. & Vallon, V. 2011. P2Y(2) receptor activation decreases blood pressure and increases renal Na(+) excretion. Am J Physiol Regul Integr Comp Physiol 301, R510-R518.
68. Rosenblum, W.I. & Nelson, G.H. 1990. Tone regulates opposing endothelium-dependent and -independent forces: resistance brain vessels in vivo. Am J Physiol Heart Circ Physiol 259, H243-H247.
69. Rosenblum, W.I., Nelson, G.H. & Weinbrecht, P. 1990. Histamine elicits competing endothelium-dependent constriction and endothelium-independent dilation in vivo in mouse cerebral arterioles. Stroke 21, 305-309.
70. Rubino, A., Ziabary, L. & Burnstock, G. 1999. Regulation of vascular tone by UTP and UDP in isolated rat intrapulmonary arteries. Eur J Pharmacol 370, 139-143.
71. Sankaranarayanan, A., Raman, G., Busch, C., Schultz, T., Zimin, P.I., Hoyer, J., Kohler, R. & Wulff, H. 2009. Naphtho[1, 2-d]thiazol-2-ylamine (SKA-31), a new activator of KCa2 and KCa3.1 potassium channels, potentiates the endothelium-derived hyperpolarizing factor response and lowers blood pressure. Mol Pharmacol 75, 281-295.
72. + channel deficiency. Proc Natl Acad Sci USA 101, 9474-9478.
73. Sausbier, M., Arntz, C., Bucurenciu, I., Zhao, H., Zhou, X.B., Sausbier, U., Feil, S., Kamm, S., Essin, K., Sailer, C.A. et al. 2005. Elevated blood pressure linked to primary hyperaldosteronism and impaired vasodilation in BK channel-deficient mice. Circulation 112, 60-68.
74. Scotland, R.S., Chauhan, S., Vallance, P.J. & Ahluwalia, A. 2001. An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Hypertension 38, 833-839.
75. Shah, M.K. & Kadowitz, P.J. 2002. Cyclic adenosine monophosphate-dependent vascular responses to purinergic agonists adenosine triphosphate and uridine triphosphate in the anesthetized mouse. J Cardiovasc Pharmacol 39, 142-149.
76. Shaver, S.R., Rideout, J.L., Pendergast, W., Douglass, J.G., Brown, E.G., Boyer, J.L., Patel, R.I., Redick, C.C., Jones, A.C., Picher, M. & Yerxa, B.R. 2005. Structure-activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors. Purinergic Signal 1, 183-191.
77. + channel. Circ Res 99, 537-544.
78. Simon, A.M. & McWhorter, A.R. 2003. Decreased intercellular dye-transfer and downregulation of non-ablated connexins in aortic endothelium deficient in connexin37 or connexin40. J Cell Sci 116, 2223-2236.
79. Sokoya, E.M., Burns, A.R., Setiawan, C.T., Coleman, H.A., Parkington, H.C. & Tare, M. 2006. Evidence for the involvement of myoendothelial gap junctions in EDHF-mediated relaxation in the rat middle cerebral artery. Am J Physiol Heart Circ Physiol 291, H385-H393.
80. Tölle, M., Schuchardt, M., Wiedon, A., Huang, T., Klöckel, L., Jankowski, J., Jankowski, V., Zidek, W. & van der Giet, M. 2010. Differential effects of uridine adenosine tetraphosphateon purinoceptors in the rat isolated perfused kidney. Br J Pharmacol 161, 530-540.
81. + T cells via purinergic P2 receptor activation. J Immunol 189, 1303-1310.
82. Vollmayer, P., Clair, T., Goding, J.W., Sano, K., Servos, J. & Zimmermann, H. 2003. Hydrolysis of diadenosine polyphosphates by nucleotide pyrophosphatases/phosphodiesterases. Eur J Biochem 270, 2971-2978.
83. Waldron, G.J. & Garland, C.J. 1994. Contribution of both nitric oxide and a change in membrane potential to acetylcholine-induced relaxation in the rat small mesenteric artery. Br J Pharmacol 112, 831-836.
84. Wihlborg, A.K., Malmsjo, M., Eyjolfsson, A., Gustafsson, R., Jacobson, K. & Erlinge, D. 2003. Extracellular nucleotides induce vasodilatation in human arteries via prostaglandins, nitric oxide and endothelium-derived hyperpolarising factor. Br J Pharmacol 138, 1451-1458.
85. de Wit, C. & Griffith, T.M. 2010. Connexins and gap junctions in the EDHF phenomenon and conducted vasomotor responses. Pflugers Arch 459, 897-914.
86. de Wit, C. & Wolfle, S.E. 2007. EDHF and gap junctions: important regulators of vascular tone within the microcirculation. Curr Pharm Biotechnol 8, 11-25.
87. de Wit, C., Roos, F., Bolz, S.S., Kirchhoff, S., Kruger, O., Willecke, K. & Pohl, U. 2000. Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res 86, 649-655.
88. Wolfle, S.E., Schmidt, V.J., Hoyer, J., Kohler, R. & de Wit, C. 2009. Prominent role of KCa3.1 in endothelium-derived hyperpolarizing factor-type dilations and conducted responses in the microcirculation in vivo. Cardiovasc Res 82, 476-483.
89. Zygmunt, P.M. & Hogestatt, E.D. 1996. Role of potassium channels in endothelium-dependent relaxation resistant to nitroarginine in the rat hepatic artery. Br J Pharmacol 117, 1600-1606.