Ulus, İsmail H.Wurtman, Richard J.2024-03-192024-03-192015-04Cansev, M. vd. (2015). "Evidence for the existence of pyrimidinergic transmission in rat brain". Neuropharmacology, 91, 77-86.0028-39081873-7064https://www.sciencedirect.com/science/article/pii/S0028390814004705https://hdl.handle.net/11452/40482The 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.eninfo:eu-repo/semantics/closedAccessNeurosciences & neurologyPharmacology & pharmacyUridineUTPUDPPyrimidinergicNeurotransmissionP2Y receptorsUridine nucleotide receptorCDP-choline levelsP2Y receptorsDocosahexaenoic acidAlzheimers-diseaseFunctional expressionPhospholipase-CNervous-systemEcto-atpaseCellsAcetylcholineAnimalsBrain chemistryCholineCorpus striatumExtracellular fluidMaleRatsRats, Sprague-DawleyReceptors, purinergic P2YUridineUridine diphosphateUridine triphosphateAcetylcholineAnimalsBrain chemistryCholineCorpus striatumExtracellular fluidMaleRatsRats, Sprague-DawleyReceptors, purinergic P2YUridineUridine diphosphateUridine triphosphateArticle0003509261000092-s2.0-8492074760577869125541414https://doi.org/10.1016/j.neuropharm.2014.12.019NeurosciencesPharmacology & pharmacyPurinergic P2Y2 receptors; Uridine adenosine tetraphosphate; AnimalsDiacylglycerolInositol trisphosphateMrs 2578Purinergic P2Y receptor antagonistPurinergic P2Y2 receptorPurinergic P2Y6 receptorPyridoxal phosphate 6 azophenyl 2',4' disulfonic acidSuraminUnclassified drugUridineUridine diphosphateUridine triphosphateAcetylcholineCholinePurinergic P2Y receptorUridineUridine diphosphateUridine triphosphateAnalysis of varianceAnimal experimentAnimal tissueArticleBrain levelCerebrospinal fluidCholinergic transmissionControlled studyCorpus striatumEnzyme analysisExtracellular fluidHigh performance liquid chromatographyHydrolysisIn vivo studyLimit of detectionMaleMembrane depolarizationMicrodialysisNeurotransmissionNonhumanPyrimidinergic transmissionRatTandem mass spectrometryAnimalBrain chemistryChemistryDrug effectsExtracellular fluidMetabolismSprague Dawley rat