GZMK and Cerebral ischemia: This insensitivity might be the result of increased expression of β-arrestin-1 during cerebral ischemia [44], which binds G-protein receptor kinase (GRK)-mediated phosphorylated form of the adrenoreceptors, preventing coupling of the receptor with G-protein, and also recruits phosphodiesterases that mediate degradation of cAMP [45]–[47].