Purinergic receptor activation inhibits mitogen-stimulated proliferation in primary neurospheres from the adult mouse subventricular zone

The expression pattern of purinergic receptors was examined in subventricular zone-derived primary neurospheres. Primary neurospheres expressed mRNA for P2X4 and P2X7 receptors, all P2Y receptors, with the exception of P2Y4, and the A1, A2a and A2b adenosine receptors. ATPγS, ADPβS and UTP evoked transient increases in cytoplasmic Ca2+ concentration in dissociated primary neurospheres, demonstrating the functional expression of P2Y1 and P2Y2 receptors. Ca2+ transients were not attenuated by the removal of extracellular Ca2+ and were reversibly inhibited by the P2Y1 selective antagonist, MRS 2179. P2Y and adenosine receptor agonists reduced the size and frequency of primary neurospheres. The effects of ADPβS and adenosine were reversed by subtype-selective receptor antagonists, demonstrating that P2Y1 and A2a receptors mediate inhibitory effects on primary neurosphere proliferation. The modulation of neural precursor cell proliferation by P2Y and adenosine receptors therefore represents a potential regulatory mechanism within the neurogenic microenvironment.