TY - JOUR
T1 - Gβγ counteracts Gαq signaling upon α1-adrenergic receptor stimulation
AU - Nishida, Motohiro
AU - Takagahara, Shuichi
AU - Maruyama, Yoshiko
AU - Sugimoto, Yoshiyuki
AU - Nagao, Taku
AU - Kurose, Hitoshi
N1 - Funding Information:
This work was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Science, and Culture, Japan. M.N. was a recipient for Japan Society for the Promotion of Science for Young Scientists.
PY - 2002/3/8
Y1 - 2002/3/8
N2 - In rat neonatal myocytes, a constitutively active Gαq causes cellular injury and apoptosis. However, stimulation of the α1-adrenergic receptor, one of the Gq 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 Gq counteracts the Gαq-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 Gq 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 Gαq-induced cellular injury and apoptosis.
AB - In rat neonatal myocytes, a constitutively active Gαq causes cellular injury and apoptosis. However, stimulation of the α1-adrenergic receptor, one of the Gq 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 Gq counteracts the Gαq-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 Gq 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 Gαq-induced cellular injury and apoptosis.
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U2 - 10.1006/bbrc.2002.6553
DO - 10.1006/bbrc.2002.6553
M3 - Article
C2 - 11866464
AN - SCOPUS:0036296769
SN - 0006-291X
VL - 291
SP - 995
EP - 1000
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -