Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2786993 | International Journal of Developmental Neuroscience | 2008 | 15 Pages |
We have used P19 embryonal carcinoma cells as in vitro model for early neurogenesis to study ionotropic P2X and metabotropic P2Y receptor-induced Ca2+ transients and their participation in induction of proliferation and differentiation. In embryonic P19 cells, P2Y1, P2Y2 and P2X4 receptors or P2X-heteromultimers with similar P2X4 pharmacology were responsible for ATP and ATP analogue-induced Ca2+ transients. In neuronal-differentiated cells, P2Y2, P2Y6, P2X2 and possibly P2X2/P2X6 heteromeric receptors were the major mediators of the elevations in intracellular free calcium concentration [Ca2+]i. We have collected evidence for the involvement of metabotropic purinergic receptors in proliferation induction of undifferentiated and neural progenitor cells by using a BrdU-incorporation assay. ATP-, UTP-, ADP-, 2-MeS-ATP- and ADP-βS-induced proliferation in P19 cells was mediated by P2Y1 and P2Y2 receptors as judged from pharmacological profiles of receptor responses. ATP-provoked acceleration of neuronal differentiation, determined by analysis of nestin and neuron-specific enolase gene and protein expression, also resulted from P2Y1 and P2Y2 receptor activation. Proliferation- and differentiation-induction involved the activation of inositol-trisphosphate sensitive intracellular Ca2+ stores.