Haas CB, Lovászi M, Braganhol E, Pacher P, Haskó G.J Immunol. 2021 May 1;206(9):1983-1990. doi: 10.4049/jimmunol.2001342.PMID: 33879578Free PMC article.Review.
Abstract
Nucleoside triphosphate diphosphohydrolases (NTPDases) are a
family of enzymes that hydrolyze nucleotides such as ATP, UTP, ADP, and
UDP to monophosphates derivates such as AMP and UMP. The NTPDase family
consists of eight enzymes, of which NTPDases 1, 2, 3, and 8 are
expressed on cell membranes thereby hydrolyzing extracellular
nucleotides.
Cell membrane NTPDases are expressed in all tissues, in
which they regulate essential physiological tissue functions such as
development, blood flow, hormone secretion, and neurotransmitter
release. They do so by modulating nucleotide-mediated purinergic
signaling through P2 purinergic receptors. NTPDases 1, 2, 3, and 8 also
play a key role during infection, inflammation, injury, and cancer.
Under these conditions, NTPDases can contribute and control the
pathophysiology of infectious,inflammatory diseases and cancer.
In this
review, we discuss the role of NTPDases, focusing on the less
understood NTPDases 2-8, in regulating inflammation and immunity during
infectious, inflammatory diseases, and cancer.
Davis CW, Lazarowski E.Respir Physiol Neurobiol. 2008 Nov 30;163(1-3):208-13. doi: 10.1016/j.resp.2008.05.015. Epub 2008 May 28.PMID: 18635403Free PMC article.Review.
At rest, ATP is released onto airway surfaces at
approximately 370fmol/mincm2, but only approximately 3% of released ATP
is recovered in ASL. Secreted UTP meets with a similar fate. A wide variety of hydrolytic and transphosphorylating ecto-enzymes convert the triphosphate …
The release of nucleotides into extracellular space is
triggered by insults like wounding and ultraviolet radiation, resulting
in stimulatory or inhibitory signals via plasma membrane nucleotide receptors. As similar insults are known to activate hyaluronan synthesis we ex …
ATP and ADP strongly inhibited LXF-289 cell proliferation.
The nucleotide potency profile was ATP = ADP = ATPgammaS > > UTP, UDP, whereas alpha,beta-methylene-ATP, beta,gamma-methylene-ATP, 2',3'-O-(4-benzoylbenzoyl)-ATP, AMP and UMP were inactive. ...I …
Renner AB, Rieger K, Grunow D, Zimmermann-Kordmann M, Gohlke M, Reutter W.Glycoconj J. 2007 Dec;24(9):531-41. doi: 10.1007/s10719-007-9048-x. Epub 2007 Jun 19.PMID: 17577663
In contrast to liver, the heart muscle uracil nucleotide
concentrations were decreased by 40%. In kidney, the sum of UTP, UDP and UMP showed a decrease of 40%, whereas UDP-sugars were increased 1.4-fold. ...Despite the 4 to 6-fold increase of UTP …
P2Y receptors (P2YRs) are a family of G protein-coupled receptors
activated by extracellularnucleotides. Physiological P2YR agonists
include purine and pyrimidine nucleoside di- and triphosphates, such as
ATP, ADP, UTP, UDP, nucleotide sugars, and dinucleotides. Eight subtypes
exist, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14,
which represent current or potential future drug targets.
Here we
provide a comprehensive overview of ligands for the subgroup of the P2YR
family that is activated by uracil nucleotides: P2Y2 (UTP, also ATP and dinucleotides), P2Y4 (UTP), P2Y6 (UDP), and P2Y14
(UDP, UDP-glucose, UDP-galactose). The physiological agonists are
metabolically unstable due to their fast hydrolysis by
ectonucleotidases. A number of agonists with increased potency,
subtype-selectivity and/or enzymatic stability have been developed in
recent years. Useful P2Y2R agonists include MRS2698 (6-01,
highly selective) and PSB-1114 (6-05, increased metabolic stability). A
potent and selective P2Y2R antagonist is AR-C118925 (10-01). For studies of the P2Y4R, MRS4062 (3-15) may be used as a selective agonist, while PSB-16133 (10-06) is a selective antagonist. Several potent P2Y6R agonists have been developed including 5-methoxyuridine 5'-O-((Rp)α-boranodiphosphate) (6-12), PSB-0474 (3-11), and MRS2693 (3-26). The isocyanate MRS2578 (10-08) is used as a selective P2Y6R
antagonist, although its reactivity and low water-solubility are
limiting. With MRS2905 (6-08), a potent and metabolically stable P2Y14R agonist is available, while PPTN (10-14) represents a potent and selective P2Y14R antagonist. The radioligand [3H]UDP can be used to label P2Y14Rs.
In addition, several fluorescent probes have been developed. Uracil
nucleotide-activated P2YRs show great potential as drug targets,
especially in inflammation, cancer, cardiovascular and neurodegenerative
diseases.
Giuliani AL, Sarti AC, Di Virgilio F.Immunol Lett. 2019 Jan;205:16-24. doi: 10.1016/j.imlet.2018.11.006. Epub 2018 Nov 12.PMID: 30439478Review.
Extracellular nucleotides, mainly ATP, but also ADP, UTP, UDP and UDP-sugars,
adenosine, and adenine base participate in the "purinergic signalling"
pathway, an ubiquitous system of cell-to-cell communication. ...
Extracellular nucleotides play a central role in the
growth and progression of a variety of cancer types - almost all tumor
cells and immune cells express purinergic membrane receptors for
extracellular nucleotides (ATP, ADP, UTP, UDP, UDP-sugar) and t …
Anderson CM, Parkinson FE.Trends Pharmacol Sci. 1997 Oct;18(10):387-92. doi: 10.1016/s0165-6147(97)01106-1.PMID: 9357323Review.
Cells can synthesize uracil nucleotides de novo or by salvage of uridine. UTP made from salvage might be preferentially used for RNA synthesis in the nucleus, while UTP synthesized de novo seems to be used for UDP-sugar and CDP-phospholipid production. …
Di Virgilio F, Adinolfi E.Oncogene. 2017 Jan 19;36(3):293-303. doi: 10.1038/onc.2016.206. Epub 2016 Jun 20.PMID: 27321181Free PMC article.Review.
Virtually, all tumor cells as well as all immune cells
express plasma membrane receptors for extracellular nucleosides
(adenosine) and nucleotides (ATP, ADP, UTP, UDP and sugarUDP). The tumor microenvironment is characterized by an unusually high conc …
The noninvasive in vivo 19F-NMR technique is particularly
advantageous, since it allows the simultaneous analysis of all dGalF
metabolites. The diversion of uridylate, due to the accumulation of UDP-2-deoxy-2-fluoro-D-hexoses, was associated with a rapid depletion of hepat …
Ohashi T, Cramer N, Ishimizu T, Hase S.Anal Biochem. 2006 May 15;352(2):182-7. doi: 10.1016/j.ab.2006.02.026. Epub 2006 Mar 15.PMID: 16581011
Here we show that UDP-sugar pyrophosphorylase from Pisum sativum with a broad specificity has UDP-GalUA pyrophosphorylase activity. ...The recombinant UDP-sugar pyrophosphorylase had optimal pH of 6.0, and the apparent K(m) values for GalUA 1-ph …
Hepatic synthesis rates of UDP-glucose and UDP-glucuronic
acid were determined in rats. Two high pressure liquid chromatographic
methods were developed to quantitate and isolate UTP, UDP-glucose, and UDP-glucuronic acid from perchloric acid extr …
1946 syntynyt Tampereella
Ylioppilastutkinto 1964 Lempäälä
Lääketietaan kandidaatti 1966 Turun yliopisto
Lääketieteen lisensiaatti 1972 Turun Yliopisto
Dietetiikan opiskelu 1998 - 2001 Göteborgin Yliopisto
Eläkkeelle 2010
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