The role of the alpha, adrenergic receptor in the restraint-induced phosphorylation of stat3.
Johnson-EA; O'Callaghan-JP; Miller-DB
Toxicologist 2003 Mar; 72(S-1):201
Stress causes physiological changes in most organ systems in intact organisms. The Janus kinases-signal transducers and activators of transcription (JAK-STAT) signaling pathways are believed to be crucial in these changes but have received limited investigation utilizing in vivo stress models. We previously showed that the restraint of mice results in a substantial activation of STAT-3 in liver but the mechanism responsible for this activation is unknown. One critical component of the response to stress involves activation of the sympathetic nervous system and release of the catecholamines epinephrine and norepinephrine. In this work we used agonists and antagonists of the alpha adrenergic receptor to examine the role of the catecholamines in the activation of STAT-3 in liver. C57Bl6J mice were restrained in centrifuge tubes (2.5 cm inner diameter) for 2 or 4 hours and killed immediately afterward by focused microwave irradiation. The phosphorylation state of STAT3 was determined by western blotting and chemiluminescence detection using phospho state-specific antibodies. In confirmation of our previous work restraint produced large increases in p-STAT3. Phentolamine, an alpha-adrenegic antagonist given (10 mg/kg s.c.) 30 minutes before the start of restraint completely blocked the phosphorylation of STAT3. Further, the alpha1-adrenergic agonist phenylephrine when given (10 mg/kg s.c.) to unrestrained mice stimulates phosphorylation of STAT3 by more than 10 fold within 2 hours of the injection. Our data suggest that catecholamines acting through alpha adrenergic receptors play a crucial role in the activation of STAT3 induced by restraint.
Stress; Physiological-effects; Physiological-response; Physiological-stress; In-vivo-studies; Models; Nervous-system; Liver; Animal-studies; Animals; Laboratory-animals
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah