Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells

doi:10.1016/0168-0102(92)90030-G

Neuroscience Research

Volume 13, Issue 1, February 1992, Pages 1-17

https://doi.org/10.1016/0168-0102(92)90030-G Get rights and content

Abstract

Aqueous extracts of the brains of 18-day-old white Leghorn chicken embryos contain several substances that stimulate proliferation of primary cultures of chick brain astrocytes. Most of the mitogens are peptides. Purification of one mitogenic fraction was obtained by centrifugation, passage through Amicon Diaflo membranes of nominal molecular weight cutoffs 30, 1 and 0.5 kDa, ion exchange chromatography and reverse phase high performance liquid chromatography (HPLC) using a Deltapak C₁₈ column. The mitogenic fraction contained to amino acids. On the basis of its behaviour on thin layer chromatography, its ultraviolet absorption spectrum, its ¹H and ³¹P nuclear magnetic resonance spectra and its behaviour on positive and negative ion fast atom bombardment mass spectrometry, the mitogenic material was identified as adenosine-5′-monophosphate (AMP). Other adenosine compounds including adenosine, ADP and ATP also stimulated proliferation of and [³H]leucine incorporation into primary cultures of astrocytes. Nitrobenzylthyioinosine (NBTI), an inhibitor of nucleoside transport, did not prevent the stimulation of [³H]leucine incorporation into cultured astrocytes. Polyadenylic acid (Poly A), that mimics the effect of adenosine at adenosine receptors, also stimulated proliferation of the astrocytes. The effects of adenosine and Poly A were not inhibited by 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) but were inhibited by 1,3-dipropyl-7-methyl-xanthine (DPMX), indicating that adenosine and Poly A acted at the cell surface, likely through adenosine A₂ receptors. The stimulatory effect of ATP was biphasic. The proliferative effect of low, but not of high, concentrations of ATP were abolished by DPMX. The purinergic P₂ receptor agonist 2-methylthioATP and, at higher concentrations, the P_2y agonist, α,β-methyleneATP also stimulated incorporation of [³H]thymidine. These data indicate that high concentrations of ATP stimulate cell proliferation through at a P₂, possibly a P_2y receptor. These results have considerable biological significance. After brain injury, or when cells in brain die or become hypoxic, nucleotides and nucleosides are released from the cells. Their extracellular concentrations can exceed those required to stimulate astrocyte proliferation in vitro. Therefore they may be partly responsible for gliotic changes following cell death in brain.

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Research reportAdenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells

Abstract

Dev. Brain Res.

J. Biol. Chem.

Dev. Brain Res.

Eur. J. Pharmacol.

Trends Pharmacol. Sci.

FEBS Lett.

Life Sci.

Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome

Science

Adenosine receptors: Roles and pharmacology

Ann. NY Acad. Sci.

Regulatory function of adenosine

Partial purification of a low-molecular weight growth factor from chicken brain

J. Cell. Physiol.

Purification of a chick brain-derived growth factor by reversed-phase high-performance liquid chromatography

J. Neurosci.

Phosphorus-31 fourier transform nuclear magnetic resonance study on mononucleotides and dinucleotides 1: chemical shifts

Biochemistry

Subtypes of P2-Purinoceptors: studies using analogues of ATP

Ann. NY Acad. Sci.

1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water soluble antagonists for A1 and A2 adenosine receptors

J. Med. Chem.

Nuclear magnetic resonance studies of 5′-ribo and deoxyribonucleotide structures

Biochemistry

Glial fibrillary acidic protein and Alzheimer-type senile dementia

Neurology

Astrocyte response to injury

The relationship between purines, pyrimidines, nucleosides and glutamine for fibroblast cell proliferation

J. Cell Physiol.

Human Tumor Cells In Vitro

Isopentenyl adenosine stimulates and inhibits mitosis of human lymphocytes treated with phytohemagglutinin

Science

Adenosine deaminase and [3H]nitrobenzylthioinosine as markers of adenosine metabolism and transport in central purinergic systems

Research report
Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells

Subtypes of P₂-Purinoceptors: studies using analogues of ATP

1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water soluble antagonists for A₁ and A₂ adenosine receptors

Adenosine deaminase and [³H]nitrobenzylthioinosine as markers of adenosine metabolism and transport in central purinergic systems