Cyclic AMP regulates G(o alpha) protein and mRNA levels by modulating the transcriptional rate of G(o alpha) gene

In fat astroglial cells, four G(o alpha) transcripts were found: G(o2 alpha ) mRNA (5.7 kb) and three G(o1 alpha) mRNAs (4.0, 3.0 and 2.3 kb). However, G(o2 alpha) but little G(o alpha 1) proteins were present in membrane-enri ched fractions. Culturing astroglial cells with forskolin (10 mu M) or isop roterenol (10 mu M) a beta-adrenergic agonist increased transiently in a ti me-dependent manner the levels of G(o alpha) proteins. The degradation rate of G(o alpha) proteins was slightly decreased by the cAMP treatment. In pa rallel, forskolin (10 mu M) treatment increased transiently the amounts of both G(o1 alpha) and G(o2 alpha) mRNAs. The relative transcription rate of G(o alpha) gene was increased by 1.7-fold in forskolin-treated cells wherea s the half-lives of G(o1 alpha) and G(o2 alpha) mRNAs were not significantl y changed. These results suggest that cAMP regulates the transcription rate of Go alpha gene and this is compatible with the existence of a cAMP respo nsive element in the promoter of the G(o alpha) gene. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.