GLUCOCORTICOIDS REGULATE THE AMOUNT OF G-PROTEINS IN RAT AORTA

Glucocorticoids are known to influence cardiovascular sensitivity to catecholamines but the molecular mechanisms are undefined. We recently showed that glucocorticoids control the coupling of adrenergic receptors to G protein. Alterations in the amount of G protein is one mechanism by which receptor-G protein coupling may be controlled. Therefore, we set out to measure the levels of G proteins in aorta from normal, adrenalectomized and dexamethasone-treated adrenalectomized rats. G proteins were measured in plasma membrane preparations by immunoblotting and horseradish peroxidase staining. After adrenalectomy there was a 53% (n = 5) decrease in the density of staining for Gi (ANOVA; P < 0.05 compared to control). Conversely, there was a 210% (n = 5) increase in the density of staining for Gs. The levels of Go and the β-subunit of G proteins were not changed by adrenalectomy. Dexamethasone-replacement treatment after adrenalectomy returned Gi and Gs close to control values. Go remained unaltered compared to controls but was 24% (n = 3) less than the adrenalectomized values (ANOVA; P < 0.05). The levels of β-subunit after dexamethasone replacement were significantly greater (ANOVA; P < 0.05) than both the controls and adrenalectomized values. These results show that glucocorticoids can differentially regulate the amounts of G proteins in rat aorta as in other tissues. This may be an important mechanism by which steroids control receptor-G protein coupling and hence transmembrane signalling pathways in vascular smooth muscle.