Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1995-4-19
pubmed:abstractText
The effects of ATP (5-500 microM) were evaluated on the proliferation rate of cultured astrocytes by measuring 3H-thymidine incorporation and by flow cytometric analysis of the cell cycle. Determinations after 16 hours showed that ATP present in the culture medium for the whole period caused a dose-dependent reduction of cell proliferation, while if the exposure to ATP was limited to the first 8 hours, the proliferation was increased (always in a dose-dependent manner). A time course study of 3H-thymidine incorporation showed that, in the presence of ATP, 3H-thymidine was incorporated at a slower rate than in controls; the replacement of the culture medium with an ATP-free fresh medium, at the 8th hour, was followed by a 3H-thymidine incorporation occurring at such a fast rate to overshoot the control values. High performance liquid chromatography (HPLC) analysis, carried out to identify purine compounds present in the culture medium during cell exposure to ATP, indicated that more than 95% of the added ATP was metabolized within 1 hr. Conversely, an increase of purine metabolites was measured, this accumulation being greater at the highest concentrations of added ATP. The presence of high levels of extracellular ATP catabolites suggested that these compounds may act on the regulation of cell replication via the different purine receptors. This hypothesis was tested and confirmed by using agonists and antagonists selective for the P1 and the P2 sites. One hundred microM 2methylthio-ATP (2MeSATP), a P2Y agonist metabolized as fast as ATP, reproduced effects very similar to the ATP-induced ones. On the other hand, the nonhydrolisable ATP analogue, adenosine 5'-(beta, gamma-imido)-triphosphate (AMP-PNP) at 100 microM, induced a mitogenic effect as well as the A2 site stimulation. On the contrary, the activation of A1 receptors by 5 microM R-phenyl-isopropyladenosine (R-PIA) inhibited astrocyte proliferation; moreover, 100 nM 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1 site antagonist, reversed the ATP-induced inhibition of cell proliferation. These results indicate that exogenous ATP, as a consequence of its rapid extracellular breakdown, exerts a dual influence on astrocyte proliferation by the involvement of both P1 and P2Y receptors. These findings might be relevant to such pathological conditions of the central nervous system (CNS), as seizures, hypoxia or ischemia, in which great amounts of purines released in the brain can influence a reactive astrocyte proliferative response to injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
556-66
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:7891391-Adenosine Triphosphate, pubmed-meshheading:7891391-Animals, pubmed-meshheading:7891391-Astrocytes, pubmed-meshheading:7891391-Cell Cycle, pubmed-meshheading:7891391-Cells, Cultured, pubmed-meshheading:7891391-Chromatography, High Pressure Liquid, pubmed-meshheading:7891391-Corpus Striatum, pubmed-meshheading:7891391-Culture Media, pubmed-meshheading:7891391-DNA Replication, pubmed-meshheading:7891391-Horses, pubmed-meshheading:7891391-Nerve Tissue Proteins, pubmed-meshheading:7891391-Purinergic P1 Receptor Agonists, pubmed-meshheading:7891391-Purinergic P1 Receptor Antagonists, pubmed-meshheading:7891391-Purinergic P2 Receptor Agonists, pubmed-meshheading:7891391-Purinergic P2 Receptor Antagonists, pubmed-meshheading:7891391-Purines, pubmed-meshheading:7891391-Rats
pubmed:year
1994
pubmed:articleTitle
Effects of exogenous ATP and related analogues on the proliferation rate of dissociated primary cultures of rat astrocytes.
pubmed:affiliation
Institute of Pharmacology and Bio-Medical Technologies, School of Medicine, University of Chieti, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't