ADENOSINE A(2B) RECEPTOR SIGNALING IS ALTERED BY STIMULATION OF BRADYKININ OR INTERLEUKIN RECEPTORS IN ASTROGLIOMA CELLS

The human astroglioma cell D384 possesses adenosine A(2B) receptors coupled to the formation of cyclic AMP. These cells also possess bradykinin B-2 receptors coupled to phospholipase C and consequent increases in intracellular calcium and protein kinase C. Interleukin 1 beta causes an increase in c-fos, AP-1 transcriptional activity and an increased expression of several genes including NGF, but the initial signalling events are unknown. Bradykinin causes a rapid decrease in A(2B) receptor mediated cAMP formation, via a mechanism that involves calcium, but nor cGMP, and appears to depend upon a direct decrease in adenylyl cyclase. II-1 beta causes a slowly developing (18-24 h) increase in A(2B) receptor signalling. The results indicate that adenosine effects in glial cells, believed to be important in neuroprotection, are modified in the short and long-term by inflammatory mediators.