Specific β ₂ AR Blocker ICI 118,551 Actively Decreases Contraction Through a G _i -Coupled Form of the β ₂ AR in Myocytes From Failing Human Heart

Abstract

We hypothesize that ICI 118,551 binding directs the beta(2)AR to a G(i)-coupled form and away from the G(s)-coupled form (ligand-directed trafficking). ICI 118,551 effectively acts as an agonist at the G(i)-coupled beta(2)AR, producing a direct negative inotropic effect. Conditions where beta(2)ARs are present and G(i) is raised (failing human heart, TGbeta(2) mouse heart) predispose to the appearance of the negative inotropic effect.