Data di Pubblicazione:
2000
Citazione:
Activation of the A(3) adenosine receptor affects cell cycle progression and cell growth / R. Brambilla, F. Cattabeni, S. Ceruti, D. Barbieri, C. Franceschi, Y. Kim, K. Jacobson, K. Klotz, M. Lohse, M.P. Abbracchio. - In: NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY. - ISSN 0028-1298. - 361:3(2000), pp. 225-234. [10.1007/s002109900186]
Abstract:
The A3 adenosine receptor has been implicated in modulation of cell growth. As a first step to the characterization of the underlying mechanisms, we exposed Chinese hamster ovary (CHO) cells transfected with the human A3 receptor (A3R-CHO) to selective A3 receptor ligands. At micromolar concentrations, the A3 agonists N6-(3-iodobenzyl)-adenosine-5'-N- methyluronamide (IB-MECA) and its 2-chloro derivative Cl-IB-MECA reduced cell number, with no effects on either parental CHO cells (not expressing any adenosine receptor), or CHO cells transfected with the human A1 receptor. Cl-IB-MECA also reduced cell number in the human HEK293 cell line transfected with the human A3 receptor cDNA as opposed to the respective untransfected wild-type cells. In A3R-CHO, agonist-induced effects were antagonized by nanomolar concentrations of A3 antagonists, including the triazoloquinazoline derivative MRS1220, the dihydropyridine derivative MRS1191, and the triazolonaphthyridine derivative L-249,313. A3 agonist- induced effects were not due to modulation of cell adhesion, nor to necrosis or apoptosis. Growth curves revealed highly impeded growth, and flow- cytometric analysis showed markedly reduced bromodeoxyuridine incorporation into nuclei. The effect on cell cycle was completely antagonized by MRS1191. Hence, activation of the human A3 receptor in A3R-CHO results in markedly impaired cell cycle progression, suggesting an important role for this adenosine receptor subtype in cell cycle regulation and cell growth.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
R. Brambilla, F. Cattabeni, S. Ceruti, D. Barbieri, C. Franceschi, Y. Kim, K. Jacobson, K. Klotz, M. Lohse, M.P. Abbracchio
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