Up4A stimulates endothelium-independent contraction of isolated rat pulmonary artery

American Journal of Physiology. Lung Cellular and Molecular Physiology
Yu GuiXi-Long Zheng

Abstract

Extracellular nucleotides, such as ATP, UDP, and UTP, regulate pulmonary vascular tone through P2X and P2Y receptors. Recently, uridine adenosine tetraphosphate (Up(4)A) was reported as a novel endothelium-derived vasoconstrictive factor. Up(4)A contains both purine and pyrimidine moieties, which potentially activate P2X and P2Y receptors. The present study examined the effect of Up(4)A on contractility of isolated rat pulmonary artery. Up(4)A at 1-100 microM stimulated contraction in a concentration-dependent manner. Up(4)A was equipotent as UTP and UDP in the endothelium-denuded artery while much more effective than UTP and UDP in endothelium-intact preparations. The vasoconstrictor effect of Up(4)A was inhibited by suramin but not IP(5)I or desensitization of P2X receptors with alpha,beta-methylene-ATP (alpha,beta-Me-ATP). Up(4)A-induced contraction was also inhibited by pretreatment with thapsigargin, nitrendipine, or EGTA but unaffected by H1152. Furthermore, unlike ATP and UTP, Up(4)A did not induce relaxation of endothelium-intact preparations precontracted with phenylephrine. These results suggest that Up(4)A is a potent vasoconstrictor, but not a vasodilator, of the rat pulmonary artery. Up(4)A likely acts through a su...Continue Reading

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Citations

Sep 3, 2013·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zhichao ZhouDaphne Merkus
May 10, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoR Clinton Webb
Nov 24, 2011·Advances in Pharmacological Sciences·Takayuki MatsumotoR Clinton Webb
Oct 16, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Zhichao ZhouDirk J Duncker
Sep 22, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takayuki MatsumotoR Clinton Webb
Jul 1, 2009·British Journal of Pharmacology·Vera JankowskiJoachim Jankowski
Sep 20, 2012·The Journal of Pharmacology and Experimental Therapeutics·Callum MitchellCharles Kennedy
Aug 14, 2012·Pharmacological Reviews·Geoffrey BurnstockJean-Pierre Timmermans
Dec 18, 2013·Pharmacological Reviews·Geoffrey Burnstock, Vera Ralevic
May 29, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Zhichao ZhouCaroline Cheng
Sep 2, 2020·Journal of the American Heart Association·Zongye CaiZhichao Zhou
Mar 11, 2016·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takayuki MatsumotoTsuneo Kobayashi
Aug 16, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yu GuiXi-Long Zheng

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