Issue Archive

#alpha#_(1)--adrenergic receptors activate AMP--activated protein kinase in rat hearts

Xu Ming, Zhao Yanting, Song Yao, Hao Tianpao, Lu Zhizhen, Han Qide, Wang Shiqiang, Zhang Youyi

Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education.Beijing 100083；China

Abstract

To test the hypothesis that AMP-activated protein kinase (AMPK) is possibly the downstream signaling molecule of certain subtypes of adrenergic receptor (AR) in the heart, we evaluated AMPK activation mediated by ARs in H9C2 cells, a rat cardiac source cell line, and rat hearts. The AMPK-#alpha# subunit and the phosphorylation level of Thr~(172)-AMPK-#alpha# subunit were subjected to Western blot analysis. Osmotic minipumps filled with norepinephrine (NE), phenylephrine (PE) or vehicle [0.01% (W/V) vitamin C solution]were implanted into male Sprague-Dawley rats subcutaneously. The pumps delivered NE or PE continuously at the rate of 0.2 mg/kg per hour. After 7-day infusion, the activity of AMPK was examined following immunoprecipitation with anti-AMPK-#alpha# antibody. At the cellular level, we found that NE elevated AMPK phosphorylation level in a dose- and time-dependent manner, with the maximal effect at 10 #mu#mol/L NE after 10-minute treatment. This effect was insensitive to propranolol, a specific #beta#-AR antagonist, but abolished by prazosin, an #alpha#_(1)-AR antagonist, suggesting that #alpha#_(1)-AR but not #beta#-AR mediated the phosphorylation of AMPK. Moreover, the results from rat models of 7-day-infusion of AR agonists demonstrated that the activity of AMPK was significantly higher in NE (7.4-fold) and PE (6.0-fold) infusion groups than that in the vehicle group (P＜0.05, n=6). On the other hand, no obvious cardiac hypertrophy and tissue fibrosis changes were observed in PE-infused rats. Taken together, our results demonstrate that #alpha#_(1)-AR stimulation enhances the activity of AMPK, indicating an important role of #alpha#_(1)-AR stimulation in the regulation of AMPK in the heart.Understanding the activation of AMPK mediated by #alpha#_(1)-AR might have clinical implications in the therapy of heart failure.

Key words: adrenergic receptor;AMP-activated protein kinase;Heart

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Xu Ming, Zhao Yanting, Song Yao, Hao Tianpao, Lu Zhizhen, Han Qide, Wang Shiqiang, Zhang Youyi. #alpha#_(1)--adrenergic receptors activate AMP--activated protein kinase in rat hearts. Acta Physiol Sin 2007; 59 (2): 175-182 (in Chinese with English abstract).