Document Detail


Regulation of proliferation of LLC-MK2 cells by nucleosides and nucleotides: the role of ecto-enzymes.
MedLine Citation:
PMID:  8687400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Using the incorporation of [methyl-3H]thymidine as a proliferation marker, the effects of various nucleosides and nucleotides on endothelial LLC-MK2 cells were studied. We found that ATP, ADP, AMP and adenosine in concentrations of 10 microM or higher stimulate the proliferation of these cells. 2. Inhibition of ecto-ATPase (EC 3.6.1.15), 5'-nucleotidase (EC 3.1.3.5) or alkaline phosphatase (EC 3.1.3.1) significantly diminished the stimulatory effect of ATP, indicating that the effect is primarily caused by adenosine and not by adenine nucleotides. Also, the effect depends only on extracellular nucleosides, since inhibition of nucleoside uptake by dipyridamole has no influence on proliferation. 3. Other purine nucleotides and nucleosides (ITP, GTP, inosine and guanosine) also stimulate cell proliferation, while pyrimidine nucleotides and nucleosides (CTP, UTP, cytidine and uridine) inhibit proliferation. Furthermore, the simultaneous presence of adenosine and any of the other purine nucleosides is not entirely additive in its effect on cell proliferation. At the same time any pyrimidine nucleoside, when added together with adenosine, has the same inhibitory effect as the pyrimidine nucleoside alone. 4. Apparently these proliferative effects are neither caused by any pharmacologically known P1-purinoceptor, nor are they mediated by cyclic AMP, cyclic GMP, or D-myo-inositol 1,4,5-trisphosphate as second messenger, nor by extracellular Ca2+. 5. Therefore, we conclude that various purine and pyrimidine nucleosides can influence the proliferation of LLC-MK2 cells by acting on putative purinergic and pyrimidinergic receptors not previously described.
Authors:
R Lemmens; L Vanduffel; H Teuchy; O Culic
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Biochemical journal     Volume:  316 ( Pt 2)     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1996 Jun 
Date Detail:
Created Date:  1996-08-20     Completed Date:  1996-08-20     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  551-7     Citation Subset:  IM    
Affiliation:
Department MBW, Biochemistry, Limburgs Universitair Centrum, Diepenbeek, Belgium.
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MeSH Terms
Descriptor/Qualifier:
5'-Nucleotidase / antagonists & inhibitors,  metabolism
Acid Anhydride Hydrolases / antagonists & inhibitors,  metabolism
Adenosine / pharmacology
Adenosine Diphosphate / analogs & derivatives,  pharmacology
Adenosine Triphosphate / pharmacology
Alkaline Phosphatase / antagonists & inhibitors,  metabolism
Animals
Cell Division / drug effects*
Cell Line
Cell Line, Transformed
Dinucleoside Phosphates / pharmacology
Dipyridamole / pharmacology
Enzyme Inhibitors / pharmacology
Hela Cells
Humans
Levamisole / pharmacology
Nucleoside-Triphosphatase
Nucleosides / pharmacology*
Nucleotides / pharmacology*
Suramin / pharmacology
Thymidine / metabolism
Triazines / pharmacology
Chemical
Reg. No./Substance:
0/Dinucleoside Phosphates; 0/Enzyme Inhibitors; 0/Nucleosides; 0/Nucleotides; 0/Triazines; 12236-82-7/Cibacron Blue F 3GA; 145-63-1/Suramin; 14769-73-4/Levamisole; 3768-14-7/adenosine 5'-methylenediphosphate; 50-89-5/Thymidine; 50304-44-4/P(1),P(5)-di(adenosine-5'-)pentaphosphate; 5542-28-9/diadenosine tetraphosphate; 56-65-5/Adenosine Triphosphate; 58-32-2/Dipyridamole; 58-61-7/Adenosine; 58-64-0/Adenosine Diphosphate; EC 3.1.3.1/Alkaline Phosphatase; EC 3.1.3.5/5'-Nucleotidase; EC 3.6.-/Acid Anhydride Hydrolases; EC 3.6.1.15/Nucleoside-Triphosphatase
Comments/Corrections

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