Evidence for the existence of pyrimidinergic transmission in rat brain

Cansev M., Orhan F., Yaylagul E. O., Isik E., Turkyilmaz M., Aydin S., ...More

NEUROPHARMACOLOGY, vol.91, pp.77-86, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 91
  • Publication Date: 2015
  • Doi Number: 10.1016/j.neuropharm.2014.12.019
  • Journal Name: NEUROPHARMACOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.77-86
  • Keywords: 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
  • Bursa Uludag University Affiliated: Yes

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. (C) 2014 Elsevier Ltd. All rights reserved.