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

作者：Thornton Claire^*; Sardini Alessandro; Carling David

来源：Journal of Biological Chemistry, 2008, 283(25): 17116-17122.

DOI：10.1074/jbc.M708987200

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.

• 出版日期2008-6-20