Glucocorticoid increases angiotensin II type 1 receptor and its gene expression.
Recently, we demonstrated that glucocorticoid potentiates inositol triphosphate production evoked by angiotensin II in vascular smooth muscle cells. To clarify this mechanism, we investigated the effects of dexamethasone on the modulation of angiotensin II type 1 receptor and on postreceptor mechanisms in vascular smooth muscle cells. The number of angiotensin II type 1 receptors began to increase after 12 hours' incubation with dexamethasone. After 48 hours, the Bmax value reached 27 +/- 3 fmol/mg protein in dexamethasone-treated cells and 15 +/- 3 fmol/mg protein in control cells. However, binding affinity did not change. A glucocorticoid antagonist, RU 38486, completely blocked these effects of dexamethasone. Also, to elucidate the effects of dexamethasone on postreceptor mechanisms, GTP analogue-induced inositol trisphosphate production in permeabilized cells was examined. Pretreatment with 1 mumol/L dexamethasone for 48 hours did not affect these inositol trisphosphate productions. Moreover, dexamethasone had no effect on the level of Gq alpha protein. Furthermore, steady-state levels of angiotensin II type 1 receptor messenger RNA were increased 2.2 +/- 0.3-fold after 30 minutes' exposure to 1 mumol/L dexamethasone and 7.8 +/- 0.4-fold after 24 hours. We conclude that glucocorticoid induced expression of the angiotensin II type 1 receptor gene and resulted in an increase in the number of angiotensin II type 1 receptors through the glucocorticoid-specific receptor, without significant effect on postreceptor systems in vascular smooth muscle cells.
Sato
A
A
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Murakami
M
M
Nakazato
Y
Y
Iwaita
Y
Y
Saruta
T
T
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000032:analysis; D015870:Gene Expression / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000032:analysis / Q000187:drug effects* / Q000235:genetics
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D003907:Dexamethasone; D015544:Inositol 1,4,5-Trisphosphate; D019204:GTP-Binding Proteins