title: Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis.
abstract: The dinucleotide uridine adenosine tetraphosphate (Up4A), which has both purine and pyrimidine moieties, was reported as a novel endothelium-derived contracting factor. Recently, growing evidence has suggested that Up4A plays an important role in regulation of the cardiovascular function. We previously demonstrated that Up4A-induced vasoconstrictions are altered in arteries from DOCA-salt hypertensive rats. We have assessed responses to Up4A shown by renal arteries from type 2 diabetic Goto-Kakizaki (GK) rats (42-46 weeks old) and identified the molecular mechanisms involved. Concentration-dependent contractions to Up4A were greater in renal arterial rings from the GK than age-matched control Wistar group. In both groups, the inhibition of nitric oxide synthase (with N (G)-nitro-L-arginine) increased the response to Up4A, whereas the inhibition of cyclooxygenase (COX) (with indomethacin) decreased the response. Specific inhibitors of COX-1 (valeroyl salicylate) and COX-2 (NS398), a thromboxane (TX) receptor (TP) antagonist (SQ29548), and P2 receptor antagonist (suramin) also decreased the response to Up4A. Protein expressions of COXs in renal arteries were greater in the GK than Wistar group. The production of TXB2 (a metabolite of TXA2) by Up4A did not differ between these groups. Concentration-dependent contractions to U46619, an agonist of the TP receptor, were greater in renal arteries from the GK than Wistar group. The expression of P2X1 and P2Y2 receptors did not differ between these groups. These results suggest that enhancement of the Up4A-induced contraction in renal arteries from GK rats may be attributable to the increased activation of COXs/TP receptor signaling.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Shun
authors.initials: S
authors.lastname: Watanabe
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Kawamura
authors.forename: Kumiko
authors.initials: K
authors.lastname: Taguchi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D015226:Dinucleoside Phosphates; D017482:Receptors, Thromboxane; C529314:uridine adenosine tetraphosphate; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
references.citation: Clin Sci (Lond). 2012 Sep;123(6):375-86
references.pmid: 22494112
references.citation: Diabetes. 2012 Aug;61(8):1978-85
references.pmid: 22688330
references.citation: IUBMB Life. 2013 Jul;65(7):623-32
references.pmid: 23671036
references.citation: Acta Physiol (Oxf). 2010 Oct;200(2):171-9
references.pmid: 20384597
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 Apr;284(4):L614-21
references.pmid: 12618423
references.citation: Am J Physiol Heart Circ Physiol. 2011 Aug;301(2):H409-17
references.pmid: 21551273
references.citation: Circulation. 2002 Nov 19;106(21):2720-6
references.pmid: 12438299
references.citation: Br J Pharmacol. 2008 Sep;155(2):217-26
references.pmid: 18574459
references.citation: Pflugers Arch. 2006 Aug;452(5):563-72
references.pmid: 16688466
references.citation: J Cardiovasc Pharmacol. 2011 Dec;58(6):654-62
references.pmid: 21885991
references.citation: Br J Pharmacol. 2010 Jul;160(5):1092-104
references.pmid: 20590603
references.citation: Atherosclerosis. 2007 May;192(1):15-24
references.pmid: 16831440
references.citation: J Mol Med (Berl). 2013 Sep;91(9):1095-107
references.pmid: 23636508
references.citation: Stroke. 2001 Feb;32(2):516-22
references.pmid: 11157191
references.citation: Pflugers Arch. 2010 May;459(6):995-1004
references.pmid: 20127126
references.citation: J Cardiovasc Pharmacol. 2010 Apr;55(4):317-32
references.pmid: 20422736
references.citation: Hypertension. 2013 May;61(5):943-7
references.pmid: 23595139
references.citation: Hypertension. 2000 Jan;35(1 Pt 1):68-75
references.pmid: 10642277
references.citation: Pflugers Arch. 2010 May;459(6):793-806
references.pmid: 20012875
references.citation: J Pharmacol Sci. 2010;112(3):299-309
references.pmid: 20168046
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L789-94
references.pmid: 21840961
references.citation: Br J Pharmacol. 2003 Sep;140(2):285-94
references.pmid: 12970107
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Jun;294(6):G1362-8
references.pmid: 18436624
references.citation: Biochem Biophys Res Commun. 2012 Jan 20;417(3):1035-40
references.pmid: 22214933
references.citation: Am J Physiol Heart Circ Physiol. 2011 Dec;301(6):H2383-94
references.pmid: 21926342
references.citation: J Physiol. 2008 Oct 15;586(20):4843-57
references.pmid: 18755753
references.citation: J Cardiovasc Pharmacol. 2002 Dec;40(6):841-53
references.pmid: 12451317
references.citation: Pflugers Arch. 2010 May;459(6):941-50
references.pmid: 20333529
references.citation: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1673-81
references.pmid: 17557920
references.citation: Br J Pharmacol. 2012 Aug;166(7):2198-208
references.pmid: 22436072
references.citation: Pflugers Arch. 2010 May;459(6):977-94
references.pmid: 20238124
references.citation: Tohoku J Exp Med. 1976 May;119(1):85-90
references.pmid: 951706
references.citation: Br J Pharmacol. 2010 Oct;161(3):527-9
references.pmid: 20880393
references.citation: Pharmacol Res. 2012 Jan;65(1):81-90
references.pmid: 21933714
references.citation: J Pharmacol Exp Ther. 2009 Apr;329(1):324-34
references.pmid: 19164460
references.citation: Br J Pharmacol. 2010 Feb 1;159(3):604-16
references.pmid: 20082610
references.citation: Pflugers Arch. 2010 Oct;460(5):825-37
references.pmid: 20635093
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L835-42
references.pmid: 15208093
references.citation: Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1850-61
references.pmid: 21856926
references.citation: Adv Pharmacol Sci. 2011;2011:435132
references.pmid: 22110488
references.citation: Curr Med Chem. 2011;18(12):1806-19
references.pmid: 21466471
references.citation: Pharmacol Res. 2013 Jan;67(1):10-7
references.pmid: 23063485
references.citation: Nat Rev Endocrinol. 2010 Dec;6(12):665-75
references.pmid: 21045787
references.citation: Pflugers Arch. 2010 May;459(6):807-16
references.pmid: 20082095
references.citation: Kidney Int. 2012 Feb;81(3):256-65
references.pmid: 21956191
references.citation: Pflugers Arch. 2012 Apr;463(4):593-602
references.pmid: 22371141
references.citation: Pharmacol Rev. 2011 Sep;63(3):471-538
references.pmid: 21752876
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Apr;294(4):L733-8
references.pmid: 18192588
references.citation: J Vasc Res. 2012;49(3):267-78
references.pmid: 22508433
references.citation: Acta Physiol (Oxf). 2011 Sep;203(1):245-51
references.pmid: 21092073
references.citation: J Mol Med (Berl). 2011 Aug;89(8):799-810
references.pmid: 21487675
references.citation: Br J Pharmacol. 2010 Oct;161(3):530-40
references.pmid: 20880394
references.citation: Nat Med. 2005 Feb;11(2):223-7
references.pmid: 15665829
references.citation: Vascul Pharmacol. 2008 Apr-Jun;48(4-6):202-7
references.pmid: 18467183
references.citation: J Clin Invest. 1990 Jun;85(6):1728-33
references.pmid: 2140836
references.citation: J Sex Med. 2011 Sep;8(9):2472-83
references.pmid: 21718448
references.citation: Mol Cell Biochem. 2005 Dec;280(1-2):35-45
references.pmid: 16311903
references.citation: Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1776-81
references.pmid: 17569882
references.citation: Cardiovasc Res. 2005 Sep 1;67(4):723-35
references.pmid: 15885672
references.citation: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1480-90
references.pmid: 17513496
references.citation: Pharmacol Res. 2012 May;65(5):497-506
references.pmid: 22425979
references.citation: Pflugers Arch. 2012 Aug;464(2):205-15
references.pmid: 22729753
references.citation: Physiol Rev. 2013 Jan;93(1):137-88
references.pmid: 23303908