Mineralcorticoids & GlucocorticoidsEdit
Many physiological and behavioral actions of angiotensin II (AngII) are mediated by the AngII Type 1 (AT1) receptor. Specifically, mineralocorticoids and glucocorticoids regulate rennin-angiotensin system components, which include the AT1 receptor. Corticosterone and dexamethasone have been proven to increase AT1 receptor levels via glucocorticoid receptor (GR) activation. This activation results in increased AngII-induced inositol triphosphate (IP3) formation. Aldosterone – an endogenous mineralocorticoid – and deoxycorticosterone-acetate (DOCA) – a synthetic mineralocorticoid – have been proven to stimulate AT1 binding at high levels but not at physiological levels. AT1 binding increases via GR activation, and without activating a mineralocorticoid receptor (MR). Although, high doses of mineralocorticoids do not significantly affect AngII-induced IP3 formation. Researchers have theorized that this is possibly a result of insufficient coupling of the AT1 receptor to its post-receptor signaling factors.
Glucocorticoids have been proven to increase mineralocorticoid-induced actions. It has been discovered that physiological levels of dexamethasone increase AT1 binding and IP3 formation, and that physiological levels of aldosterone are primarily responsible for MR activation. However, low level combinations of each of these do not increase the effect of dexamethasone on AT1 binding. However, there has been no observed synergy between aldosterone and dexamethasone at the AT1 binding sites or in IP3 formation levels.
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