Activation of A1 and A2a adenosine receptors promotes neural progenitor cell proliferation

Abstract

Neural progenitor cells (NPCs) play a key role not only in the maintenance of the adult central nervous system (CNS) but also in the ability to recover from injury and disease. In this study, we established a 96-well-based screening system to screen small molecules modulating the proliferation of NPCs. A compound library composed of 1280 compounds was screened. We found that the A₁ adenosine receptor agonist cyclopentyladenosine (CPA) and the A_2a adenosine receptor agonist CGS-21680 increased proliferation of NPCs. The A₁ adenosine receptor agonist-induced cell proliferation was attenuated by A₁ adenosine receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). Accordingly, the A_2a adenosine receptor agonist-induced cell proliferation was attenuated by A_2a adenosine receptor antagonist SCH-58261. Further study indicated that CPA and CGS-21680 treatment induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and CPA-induced or CGS-21680-induced cell proliferation was inhibited by ERK and Akt inhibitors. These results suggested that the activation of A₁ and A_2a adenosine receptor stimulated the proliferation of NPCs via the ERK and Akt signaling pathways.

Keywords: 96-well-based screening system; A(1)/A(2a) adenosine receptors; Akt; ERK; Neural progenitor cell.