title: cCMP and cUMP occur in vivo.
abstract: Mammalian cells contain the cyclic pyrimidine nucleotides cCMP and cUMP. It is unknown whether these tentative new second messenger molecules occur in vivo. We used high performance liquid chromatography quadrupole tandem mass spectrometry to quantitate nucleoside 3',5'-cyclic monophosphates. cCMP was detected in all organs studied, most notably pancreas, spleen and the female reproductive system. cUMP was not detected in organs, probably due to the intrinsically low sensitivity of mass spectrometry to detect this molecule and organ matrix effects. Intratracheal infection of mice with recombinant Pseudomonas aeruginosa harboring the nucleotidyl cyclase toxin ExoY massively increased cUMP in lung. The identity of cCMP and cUMP in organs was confirmed by high performance liquid chromatography quadrupole time of flight mass spectrometry. cUMP also appeared in serum, urine and faeces following infection. Taken together, this report unequivocally shows for the first time that cCMP and cUMP occur in vivo.
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: baehre.heike@mh-hannover.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Bähre
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: hartwig.christina@mh-hannover.de.
authors.forename: Christina
authors.initials: C
authors.lastname: Hartwig
authors.affiliation: Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: munder.antje@mh-hannover.de.
authors.forename: Antje
authors.initials: A
authors.lastname: Munder
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: wolter.sabine@mh-hannover.de.
authors.forename: Sabine
authors.initials: S
authors.lastname: Wolter
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: stelzer.tane@mh-hannover.de.
authors.forename: Tane
authors.initials: T
authors.lastname: Stelzer
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: Schirmer.bastian@mh-hannover.de.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schirmer
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: beckert-ulrike81@email.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Beckert
authors.affiliation: Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: frankd@mcw.edu.
authors.forename: Dara W
authors.initials: DW
authors.lastname: Frank
authors.affiliation: Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: tuemmler.burkhard@mh-hannover.de.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tümmler
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: kaever.volkhard@mh-hannover.de.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Institute of Pharmacology, Hannover Medical School, D-30625 Hannover, Germany. Electronic address: seifert.roland@mh-hannover.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Seifert
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003563:Cyclic CMP / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009712:Nucleotides, Cyclic / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D053719:Tandem Mass Spectrometry; D014542:Uridine Monophosphate / Q000378:metabolism*
chemical_list: D009712:Nucleotides, Cyclic; D003563:Cyclic CMP; C045338:cyclic 3',5'-uridine monophosphate; D014542:Uridine Monophosphate
keywords: Cyclic pyrimidine nucleotides; ExoY; Mass spectrometry; Pseudomonas aeruginosa
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