α1-adrenergic receptors activate AMP-activated protein kinase in rat hearts
10.3321/j.issn:0371-0874.2007.02.011
- VernacularTitle:α1-肾上腺素受体激活大鼠心脏腺苷酸活化蛋白激酶
- Author:
Ming XU
1
;
Yan-Ting ZHAO
;
Yao SONG
;
Tian-Pao HAO
;
Zhi-Zhen LU
;
Qi-De HAN
;
Shi-Qiang WANG
;
You-Yi ZHANG
Author Information
1. 北京大学医学部附属第三医院(北医三院)
- Keywords:
adrenergic receptor;
AMP-activated protein kinase;
heart
- From:
Acta Physiologica Sinica
2007;59(2):175-182
- CountryChina
- Language:Chinese
-
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-α subunit and the phosphorylation level of Thr172-AMPK-αt 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-α 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 μmol/L NE after 10-minute treatment. This effect was insensitive to propranolol, a specific β-AR antagonist, but abolished by prazosin, an α1-AR antagonist, suggesting that α1-AR but not β-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 α1-AR stimulation enhances the activity of AMPK, indicating an important role of α1-AR stimulation in the regulation of AMPK in the heart.Understanding the activation of AMPK mediated by α1-AR might have clinical implications in the therapy of heart failure.
