700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ ReadersThis Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)
Review Article Open Access
Typically AngII the octapeptide hormone produced by the renin angiotensin system binds to angiotensin II type 1 receptor (AT1R) and activates its functions which can be competitively inhibited by AT1R blockers (ARBs). However several studies have demonstrated ligandindependently activated AT1R in clinical setting such as mechanical stretch and auto-antibodies as well as receptor mutations. Clinically used ARBs prevent ligand-independent activation of the AT1R by inverse agonistic effect with variable efficacies. Ligand-independent transition of AT1R to activated state is known to attenuate inverse agonistic efficacy of the ARBs but the molecular mechanism is unknown. Therefore, identifying the molecular basis of reduced inverse agonist efficacy of ARBs for the active-state of the AT1R provided a fundamental insight for application of ARBs in treatment of diseases as well as for future drug development. Since AT1R is an extensively studied member of G-protein coupled receptor superfamily encoded in human genome the new regulatory mechanisms of inverse agonist function we describe is relevant to disorders caused by other members of this superfamily. In this review, we focus on the molecular mechanism of attenuated inverse agonism of the ARBs.
Angiotensin II, G-protein coupled receptor, Inverse agonist, Active state, Pharmacy Practice, Clinical Pharmacy, Patient care