In Vivo β-Adrenergic Stimulation Leads to Biphasic Regulation of Giα-2 Gene Transcriptional Activity in Rat Heart

The Giα-2 gene transcriptional activity is increased by 40% in ventricular nuclei of rats stimulated in vivo with the β-adrenoceptor agonist isoprenaline for 96 h. In the present study the time course of this regulation was investigated using in vitro transcription assays with ventricular nuclei of rats treated for 12.48 and 96 h, respectively with isoprenaline (2.4 mg/kg per day) or with 0.9% NaCl as control. Whereas the Giα-2 gene specific hybridization was unchanged in ventricular nuclei after isoprenaline stimulation for 12 h the same treatment led to a 37% decrease of Giα-2 gene transcriptional activity after 48 h and to a 45% increase after 96 h. The β-adrenoceptor antagonist propranolol antagonized both the isoprenaline induced reduction and induction of Giα-2 gene transcriptional activity. There was no change in Gsαgene transcriptional activity in the respective groups. In conclusion, these results show that in rat heart in vivo β-adrenergic stimulation regulates Giα-2 gene transcription in a biphasic manner, i.e. a transient decrease is followed by an increase in transcriptional activity. This biphasic regulation by a single stimulus might be due to complex modulations of gene expression by transcription factors.