In vivo beta-adrenergic stimulation leads to biphasic regulation of Gi alpha-2 gene transcriptional activity in rat heart.

The G1 alpha-2 gene transcriptional activity is increased by 40% in ventricular nuclei of rats stimulated in vivo with the beta-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 G1 alpha-2 gene specific hybridization was unchanged in ventricular nuclei after isoprenaline stimulation for 12 h the same treatment led to a 37% decrease of G1 alpha-2 gene transcriptional activity 48 h and to a 45% increase after 96 h. The beta-adrenoceptor antagonist propranolol antagonized both the isoprenaline induced reduction and induction of G1 alpha-2 gene transcriptional activity. There was no change in Gs alpha gene transcriptional activity in the respective groups. In conclusion, these results show that in rat heart in vivo beta-adrenergic stimulation regulates G1 alpha-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.