External cyclic AMP-dependent protein kinase activity in rat C-6 glioma cells

Abstract

IN certain eukaryotic cells β-agonistic catecholamines bind to membrane-associated hormone receptors, and stimulate the intracellular synthesis of cyclic AMP by activation of the adenylate cyclase¹. In C-6 rat glioma cells stimulated with noradrenaline this increase of cyclic AMP leads to, or is correlated with, a morphological change in the cells². When the intracellular cyclic AMP concentration has reached a maximum, it returns to basal values² due to an energy-dependent excretion of cyclic AMP from the cell into the external medium^3,4, similar to that found in several mammalian systems^5–7. It is possible that the excreted cyclic AMP interacts either with an external, glial-membrane bound cyclic AMP receptor or with the surface of the surrounding cells, for example neurones. We report here that intact, cultured glial cells seem to have a cyclic AMP-dependent protein kinase on their external surface which transfers γ-phosphate of ATP to an external acceptor protein (histone). This protein kinase activity is stimulated indirectly by the addition of noradrenaline to the cells. The physiological significance of this process is unknown.