Muscarinic receptor activation of AMP-activated protein kinase inhibits orexigenic neuropeptide mRNA expression

被引：29

作者：

Thornton, Claire ^{[1
]}

Sardini, Alessandro ^{[1
]}

Carling, David ^{[1
]}

机构：

[1] Ctr Clin Sci, MRC, Cellular Stress Grp, London W12 0NN, England

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 25期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

D O I：

10.1074/jbc.M708987200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

AMP-activated protein kinase (AMPK) plays a crucial role in both cellular and whole body energy homeostasis. Here we demonstrate that the muscarinic receptor agonist carbachol activates AMPK alpha 1-containing complexes in the human SH-SY5Y cell line via a mechanism specific for the AMPK upstream kinase, Ca2+/calmodulin-dependent protein kinase kinase beta. Activation of AMPK inhibits mRNA expression of the orexigenic neuropeptides Agouti-related peptide and melanin-concentrating hormone but surprisingly has no effect on neuropeptide Y mRNA, a neuropeptide previously shown to be regulated by AMPK. Rather than restoring mRNA levels to baseline, pharmacological inhibition of Ca2+/calmodulin-dependent protein kinase kinase beta or AMPK greatly increases Agouti-related peptide and melanin-concentrating hormone mRNA expression. These data support a hypothesis that modulating basal AMPK activity in the hypothalamus is essential for maintaining tight regulation of pathways contributing to food intake.

引用

页码：17116 / 17122

页数：7

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