Inhibition of nitrobenzylthioinosine-sensitive adenosine transport by elevated D-glucose involves activation of P2Y2 purinoceptors in human umbilical vein endothelial cells

Circulation Research
J ParodiL Sobrevia

Abstract

Chronic incubation with elevated D-glucose reduces adenosine transport in endothelial cells. In this study, exposure of human umbilical vein endothelial cells to 25 mmol/L D-glucose or 100 micromol/L ATP, ATP-gamma-S, or UTP, but not ADP or alpha,beta-methylene ATP, reduced adenosine transport with no change in transport affinity. Inhibition of transport by D-glucose, ATP, and ATP-gamma-S was associated with reduced maximal binding, with no changes in the apparent dissociation constant for nitrobenzylthioinosine (NBMPR). A significant reduction (approximately 60+/-10%, P<0.05; n=6) in the number of human equilibrative NBMPR-sensitive nucleoside transporters (hENT1s) per cell (1.8+/-0.1x10(6) in 5 mmol/L D-glucose) and in hENT1 mRNA levels was observed in cells exposed to D-glucose or ATP-gamma-S. Incubation with elevated D-glucose, but not with D-mannitol, increased the ATP release by 3+/-0.2-fold. The effects of D-glucose and nucleotides on the number and activity of hENT1 and hENT1 mRNA were blocked by reactive blue 2 (nonspecific P2Y purinoceptor antagonist), suramin (Galpha(s) protein inhibitor), or hexokinase but not by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (nonselective P2 purinoceptor antagonist). Our fin...Continue Reading

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Citations

Mar 28, 2008·Purinergic Signalling·David Erlinge, Geoffrey Burnstock
Nov 13, 2003·European Journal of Pharmacology·Lara M MangraviteKathleen M Giacomini
Nov 21, 2002·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Miguel A CabritaCarol E Cass
Jan 12, 2007·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Adam N ElwiCarol E Cass
Sep 25, 2009·World Journal of Gastroenterology : WJG·Jeff Huaqing Ye, Vazhaikkurichi M Rajendran
Nov 17, 2009·Cellular and Molecular Life Sciences : CMLS·Chanyuan TanDavid Erlinge
Apr 28, 2010·Archives of Physiology and Biochemistry·Bárbara RückerEmerson A Casali
Apr 5, 2008·Biochemical and Biophysical Research Communications·Fariborz ParandehAlbert Salehi
Mar 8, 2006·The FEBS Journal·Maria G TozziPiero L Ipata
Jan 31, 2006·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Eleonora SgambatiGherardo Gheri
Oct 26, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Daniel L Sparks, Cynthia Chatterjee
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Jun 13, 2020·Frontiers in Endocrinology·Miguel Martin-Aragon BaudelManuel F Navedo
Jul 1, 2020·Cellular and Molecular Life Sciences : CMLS·Madeline Nieves-CintrónManuel F Navedo
Dec 10, 2020·International Journal of Molecular Sciences·Claudia Giuseppina FrestaClaudio Bucolo

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