title: Glucocorticoids regulate the amount of G proteins in rat aorta.
abstract: 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 53% (n = 5) decrease in the density of staining for Gi (ANOVA; P less than 0.05 compared to controls). Conversely, there was a 210% (n = 5) increase in the density of staining for Gs. The levels of Go and the beta-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 less than 0.05). The levels of beta-subunit after dexamethasone replacement were significantly greater (ANOVA; P less than 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.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Oxford.
authors.forename: R M
authors.initials: RM
authors.lastname: Haigh
authors.forename: C T
authors.initials: CT
authors.lastname: Jones
authors.forename: G
authors.initials: G
authors.lastname: Milligan
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D003907:Dexamethasone; D019204:GTP-Binding Proteins