Evidence for the existence of pyrimidinergic transmission in rat brain. (April 2015)

• Record Type: Journal Article
• Authors: Cansev, Mehmet; Orhan, Fulya; Yaylagul, Esra O.; Isik, Esra; Turkyilmaz, Mesut; Aydin, Sami; Gumus, Abdullah; Sevinc, Cansu; Coskun, Necdet; Ulus, Ismail H.; Wurtman, Richard J.
• Is Part Of: Neuropharmacology. Volume 91(2015)
• Page Start: 77
• Page End: 86
• Publication Date: 2015-04
• Subjects: Uridine -- UTP -- UDP -- Pyrimidinergic -- Neurotransmission -- P2Y receptors; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2014.12.019
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: The uridine nucleotides UTP and UDP are detected in brain ECF of rats under basal conditions. ECF concentrations of UTP and UDP can be enhanced by exogenous uridine administration. Neuronal activity enhances while blockade of depolarization reduces these concentrations. Enhanced extracellular UTP is associated with increased cholinergic neurotransmission. P2Y2 receptors mediate this effect.