title: Evidence for the existence of pyrimidinergic transmission in rat brain.
abstract: 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.
authors.affiliation: Department of Pharmacology, Uludag University School of Medicine, Bursa, Turkey. Electronic address: mcansev@uludag.edu.tr.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.affiliation: Department of Pharmacology, Uludag University School of Medicine, Bursa, Turkey.
authors.forename: Fulya
authors.initials: F
authors.lastname: Orhan
authors.affiliation: Department of Biology, Uludag University School of Arts and Sciences, Bursa, Turkey.
authors.forename: Esra O
authors.initials: EO
authors.lastname: Yaylagul
authors.affiliation: Department of Chemistry, Uludag University School of Arts and Sciences, Bursa, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Isik
authors.affiliation: Department of Pharmacology, Uludag University School of Medicine, Bursa, Turkey.
authors.forename: Mesut
authors.initials: M
authors.lastname: Turkyilmaz
authors.affiliation: Department of Pharmacology, Uludag University School of Medicine, Bursa, Turkey.
authors.forename: Sami
authors.initials: S
authors.lastname: Aydin
authors.affiliation: Uludag University School of Medicine, Bursa, Turkey.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Gumus
authors.affiliation: Department of Pharmacology, Uludag University School of Medicine, Bursa, Turkey.
authors.forename: Cansu
authors.initials: C
authors.lastname: Sevinc
authors.affiliation: Department of Chemistry, Uludag University School of Arts and Sciences, Bursa, Turkey.
authors.forename: Necdet
authors.initials: N
authors.lastname: Coskun
authors.affiliation: Department of Pharmacology, Acibadem University School of Medicine, Istanbul, Turkey.
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Ulus
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wurtman
mesh_terms: D000109:Acetylcholine / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry; D002794:Choline / Q000032:analysis; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D045604:Extracellular Fluid / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D014529:Uridine / Q000494:pharmacology; D014530:Uridine Diphosphate / Q000032:analysis*; D014544:Uridine Triphosphate / Q000032:analysis*
chemical_list: D058470:Receptors, Purinergic P2Y; D014530:Uridine Diphosphate; D002794:Choline; D000109:Acetylcholine; D014544:Uridine Triphosphate; D014529:Uridine
keywords: Neurotransmission; P2Y receptors; Pyrimidinergic; UDP; UTP; Uridine