G beta gamma counteracts G alpha(q) signaling upon alpha(1)-adrenergic receptor stimulation.
In rat neonatal myocytes, a constitutively active G alpha(q) causes cellular injury and apoptosis. However, stimulation of the alpha(1)-adrenergic receptor, one of the G(q) protein-coupled receptors, with phenylephrine for 48 h causes little cellular injury and apoptosis. Expression of the G beta gamma-sequestering peptide beta ARK-ct increases the phenylephrine-induced cardiac injury, indicating that G beta gamma released from G(q) counteracts the G alpha(q)-mediated cellular injury. Stimulation with phenylephrine activates extracellular signal-regulated kinase (ERK) and Akt, and activation is significantly blunted by beta ARK-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 G beta gamma released from G(q) upon alpha(1)-adrenergic receptor stimulation activates ERK and Akt. However, activation of Akt but not ERK plays an important role in the protection against the G alpha(q)-induced cellular injury and apoptosis.
Nishida
Motohiro
M
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Science, University of Tokyo, Tokyo 113-0033, Japan.
Takagahara
Shuichi
S
Maruyama
Yoshiko
Y
Sugimoto
Yoshiyuki
Y
Nagao
Taku
T
Kurose
Hitoshi
H
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002352:Carrier Proteins / Q000494:pharmacology; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010455:Peptides; D010656:Phenylephrine / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011994:Recombinant Proteins; D015398:Signal Transduction
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins; D020928:Mitogen-Activated Protein Kinases; D010455:Peptides; D010656:Phenylephrine; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D018340:Receptors, Adrenergic, alpha-1; D011994:Recombinant Proteins; C118981:G-protein Beta gamma; C445259:beta-adrenergic receptor kinase inhibitory peptide; C494920:Akt1 protein, rat