Novel adenosine and cAMP signalling pathways in migrating glial cells

This study was aimed at characterizing the effect of purinergic transmission on migration of embryonic ciliary ganglion satellite glial cells. Application of adenosine significantly decreased the rate of migration of glial cells whereas no differences were observed in the presence of ATP. The A_2B receptor antagonist reverted this action, but application of an A_2A receptor antagonist or a cAMP-protein kinase inhibitor had no effect on the agonist's stimulation. Forskolin, which stimulates adenylate cyclase activity, and the cAMP analogue 8-CPT-2'-O-Me-cAMP, which selectively activates the guanine exchange factor Epac1, mimicked the effect of adenosine.In addition, intracellular calcium measurements studies revealed that application of either adenosine or ATP induced an increase in [Ca²⁺]_i and that the adenosine-induced [Ca²⁺]_i response was due to Ca²⁺ entry and was blocked by an A_2A receptor antagonist, SCH 58261, or by high Gd³⁺ concentrations. Furthermore, forskolin, but not 8-CPT-2'-O-Me-cAMP, activated the Ca²⁺ entry which was blocked by Gd³⁺ and was independent of cAMP-protein kinase activity.These results demonstrate the involvement of purinergic P1 signalling in the regulation of cellular migration, and point to the importance of adenosine as a negative modulator of migration of peripheral developing glial cells and as an activator of Ca²⁺ entry.