Evidence for the existence of pyrimidinergic transmission in rat brain

被引:12
作者
Cansev, Mehmet [1 ]
Orhan, Fulya [1 ]
Yaylagul, Esra O. [2 ]
Isik, Esra [3 ]
Turkyilmaz, Mesut [1 ]
Aydin, Sami [1 ]
Gumus, Abdullah [4 ]
Sevinc, Cansu [1 ]
Coskun, Necdet [3 ]
Ulus, Ismail H. [5 ]
Wurtman, Richard J. [6 ]
机构
[1] Uludag Univ, Dept Pharmacol, Sch Med, TR-16059 Bursa, Turkey
[2] Uludag Univ, Dept Biol, Sch Arts & Sci, TR-16059 Bursa, Turkey
[3] Uludag Univ, Dept Chem, Sch Arts & Sci, TR-16059 Bursa, Turkey
[4] Uludag Univ, Sch Med, TR-16059 Bursa, Turkey
[5] Acibadem Univ, Sch Med, Dept Pharmacol, Istanbul, Turkey
[6] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
关键词
Uridine; UTP; UDP; Pyrimidinergic; Neurotransmission; P2Y receptors; URIDINE NUCLEOTIDE RECEPTOR; CDP-CHOLINE LEVELS; P2Y RECEPTORS; DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; FUNCTIONAL EXPRESSION; PHOSPHOLIPASE-C; NERVOUS-SYSTEM; ECTO-ATPASE; CELLS;
D O I
10.1016/j.neuropharm.2014.12.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The uridine nucleotides uridine-5'-triphosphate (UTP) and uridine-5'-diphosphate (UDP) have previously been identified in media from cultured cells. However, no study to date has demonstrated their presence in brain extracellular fluid (ECF) obtained in vivo. Using a novel method, we now show that UTP and UDP, as well as uridine, are detectable in dialysates of striatal ECF obtained from freely-moving rats. Intraperitoneal (i.p.) administration of uridine or exposure of striatum to depolarizing concentrations of potassium chloride increases extracellular uridine, UTP and UDP, while tetrodotoxin (TTX) decreases their ECF levels. Uridine administration also enhances cholinergic neurotransmission which is accompanied by enhanced brain levels of diacylglycerol (DAG) and inositol trisphosphate (IP3) and blocked by suramin, but not by PPADS (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) or MRS2578 suggesting a possible mediation of P2Y2 receptors activated by UTP. These observations suggest that uridine, UTP and UDP may function as pyrimidinergic neurotransmitters, and that enhancement of such neurotransmission underlies pharmacologic effects of exogenous uridine on the brain. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:77 / 86
页数:10
相关论文
共 50 条
[1]   International union of pharmacology LVIII: Update on the P2Y G protein-coupled nucleotide receptors: From molecular mechanisms and pathophysiology to therapy [J].
Abbracchio, Maria P. ;
Burnstock, Geoffrey ;
Boeynaems, Jean-Marie ;
Barnard, Eric A. ;
Boyer, Jose L. ;
Kennedy, Charles ;
Knight, Gillian E. ;
Fumagalli, Marta ;
Gachet, Christian ;
Jacobson, Kenneth A. ;
Weisman, Gary A. .
PHARMACOLOGICAL REVIEWS, 2006, 58 (03) :281-341
[2]   Purinergic signalling: Pathophysiological roles [J].
Abbracchio, MP ;
Burnstock, G .
JAPANESE JOURNAL OF PHARMACOLOGY, 1998, 78 (02) :113-145
[3]   Loss of P2Y2 Nucleotide Receptors Enhances Early Pathology in the TgCRND8 Mouse Model of Alzheimer's Disease [J].
Ajit, Deepa ;
Woods, Lucas T. ;
Camden, Jean M. ;
Thebeau, Christina N. ;
El-Sayed, Farid G. ;
Greeson, Glen W. ;
Erb, Laurie ;
Petris, Michael J. ;
Miller, Douglas C. ;
Sun, Grace Y. ;
Weisman, Gary A. .
MOLECULAR NEUROBIOLOGY, 2014, 49 (02) :1031-1042
[4]   Regulation of brain capillary endothelial cells by P2Y receptors coupled to Ca2+, phospholipase C and mitogen-activated protein kinase [J].
Albert, JL ;
Boyle, JP ;
Roberts, JA ;
Challiss, RAJ ;
Gubby, SE ;
Boarder, MR .
BRITISH JOURNAL OF PHARMACOLOGY, 1997, 122 (05) :935-941
[5]   P2Y receptors contribute to ATP-induced increases in intracellular calcium in differentiated but not undifferentiated PC12 cells [J].
Arslan, G ;
Catalin, CM ;
Irenius, E ;
Kull, B ;
Clementi, E ;
Allgaier, C ;
Erlinge, D ;
Fredholm, BB .
NEUROPHARMACOLOGY, 2000, 39 (03) :482-496
[6]   Structure-activity relationships of anthraquinone derivatives derived from bromaminic acid as inhibitors of ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) [J].
Baqi, Younis ;
Weyler, Stefanie ;
Iqbal, Jamshed ;
Zimmermann, Herbert ;
Mueller, Christa E. .
PURINERGIC SIGNALLING, 2009, 5 (01) :91-106
[7]   Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death [J].
Burnstock, G. ;
Verkhratsky, A. .
CELL DEATH & DISEASE, 2010, 1 :e9-e9
[8]   Purinergic signalling: From normal behaviour to pathological brain function [J].
Burnstock, Geoffrey ;
Kruegel, Ute ;
Abbracchio, Maria P. ;
Illes, Peter .
PROGRESS IN NEUROBIOLOGY, 2011, 95 (02) :229-274
[9]   P2Y2 nucleotide receptors enhance α-secretase-dependent amyloid precursor protein processing [J].
Camden, JM ;
Schrader, AM ;
Camden, RE ;
González, FA ;
Erb, L ;
Seye, CI ;
Weisman, GA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) :18696-18702
[10]   Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils [J].
Cansev, M. ;
Wurtman, R. J. .
NEUROSCIENCE, 2007, 148 (02) :421-431