Gβγ counteracts Gα_q signaling upon α₁-adrenergic receptor stimulation

In rat neonatal myocytes, a constitutively active Gα_q causes cellular injury and apoptosis. However, stimulation of the α₁-adrenergic receptor, one of the G_q protein-coupled receptors, with phenylephrine for 48 h causes little cellular injury and apoptosis. Expression of the Gβγ-sequestering peptide βARK-ct increases the phenylephrine-induced cardiac injury, indicating that Gβγ released from G_q counteracts the Gα_q-mediated cellular injury. Stimulation with phenylephrine activates extracellular signal-regulated kinase (ERK) and Akt, and activation is significantly blunted by βARK-ct. Inhibition of Akt by inhibitors of phosphatidylinositol 3-kinase increases the cellular injury induced by phenylephrine stimulation. In contrast to the inhibition of Akt, inhibition of ERK does not affect the phenylephrine-induced cardiac injury. These results suggest that Gβγ released from G_q upon α1-adrenergic receptor stimulation activates ERK and Akt. However, activation of Akt but not ERK plays an important role in the protection against the Gα_q-induced cellular injury and apoptosis.