Enhanced degradation of stimulatory G-protein (Gs alpha) by cholera toxin is mediated by ADP-ribosylation of Gs alpha protein but not by increased cyclic AMP levels.

Cholera toxin (CT) catalyses ADP-ribosylation of the alpha-subunit of stimulatory protein (Gs) leading to stimulation of adenylyl cyclase and elevated intracellular cAMP. Persistent treatment (24-48 h) of C6 glioma cells with cholera toxin (100 ng/ml) caused marked downregulation of Gs alpha (75-80%) which could not be mimicked by dibutyryl cAMP (1 mM) and forskolin (10 microM) over the same time periods suggesting that CT-mediated Gs alpha downregulation is independent of cAMP production. However, CT increased the expression of Gq/11 alpha proteins at 24 and 48 h of treatment. The increase in mRNA levels of Gq/11 alpha proteins preceded the increase in Gq/11 proteins. Such stimulatory effects of CT were mimicked by forskolin and dibutyryl-cAMP. These results suggest that CT-mediated downregulation of Gs alpha is independent of cAMP but CT upregulates the expression of Gq/11 alpha proteins in a cAMP-dependent manner.