Activation of the A3 adenosine receptor affects cell cycle progression and cell growth

Roberta Brambilla, Flamino Cattabeni, Stefania Ceruti, Daniela Barbieri, Claudio Franceschi, Yong Chul Kim, Kenneth A. Jacobson, Karl Norbert Klotz, Martin J. Lohse, Maria P. Abbracchio

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Issue number3
Publication statusPublished - 2000


  • Adenosine
  • Adenosine receptor
  • Cell cycle
  • Cell growth modulation
  • CHO transfected cells
  • HEK293 transfected cells
  • Human A

ASJC Scopus subject areas

  • Pharmacology


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