We investigated the role of the A(3) adenosine receptor in cells of the astroglial lineage (both rat primary astrocytes and human astrocytoma ADF cells) by means of the selective A(3) agonists N-6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) and CI-IB-MECA, and by utilizing the selective AS receptor antagonist MRS1191. Exposure of ADF cells to mu M concentrations of either agonist resulted in reduction of cell number, likely due to cell death. In both rat astrocytes and human astrocytoma cells, at concentrations 2-3 orders of magnitude lower (which were not associated with cytotoxicity), these same agonists induced a marked reorganization of the cytoskeleton, with appearance of stress fibers and numerous cell protrusions. Functionally, these morphological changes were associated with cell protection, as demonstrated by a significant reduction of spontaneous apoptosis in A(3) agonist-treated cells. To confirm a role for the A(3) receptor in this effect, MRS1191 completely counteracted CI-IB-MECA-induced reduction of spontaneous apoptosis. In ADF cells, Ay agonists also induced changes in the intracellular distribution of the anti-apoptotic protein Bcl-X-L which became localized in cell protrusions. Also, this effect was specifically antagonized by MRS1191. These dual actions of A(3) agonists in vitro may have important in vivo implications. For example, a robust and acute activation of the A(3) receptor following massive adenosine release during ischemia may contribute to brain cell death; conversely, a subthreshold activation of this receptor prior to ischemia may trigger protective mechanisms (i.e., induction of stress fibers and of a Bcl-X-L-dependent reorganization of cytoskeleton) making the brain more resistant to subsequent insults ("ischemic tolerance").
Adenosine A3 receptor and viability of astrocytes / M.P. Abbracchio, S. Ceruti, R. Brambilla, D. Barbieri, C. Franceschi, A.M. Giammarioli, K.A. Jacobson, F. Cattabeni, W. Malorni. - In: DRUG DEVELOPMENT RESEARCH. - ISSN 0272-4391. - 45:3-4(1998 Nov), pp. 379-386. ((Intervento presentato al 6. convegno International Symposium on Adenosine and Adenine Nucleotides, New Frontiers in the 3rd-Millennium tenutosi a Ferrara nel 1998.
|Titolo:||Adenosine A3 receptor and viability of astrocytes|
ABBRACCHIO, MARIA PIA (Corresponding)
CERUTI, STEFANIA MARIA (Secondo)
|Parole Chiave:||adenosine A3 receptors; astrocytes; rat; human; cell survival|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||nov-1998|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/(SICI)1098-2299(199811/12)45:3/4<379::AID-DDR38>3.0.CO;2-Y|
|Appare nelle tipologie:||01 - Articolo su periodico|
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