AMP-Activated Protein Kinase Is Activated by the Stimulations of Gq-Coupled Receptors☆

Abstract The AMP-activated protein kinase (AMPK) functions as a metabolic sensor that monitors cellular AMP and ATP levels. Platelet-activating factor (PAF) activates endogeneous AMPKα1 in Chinese hamster ovary cells expressing the PAF receptor coupled with both G i and G q , but its activity was not inhibited after treatment with islet-activating protein. Norepinephrine and bradykinin also activated AMPKα1 in cells expressing the G q -coupled α 1b -adrenergic receptor and bradykinin receptor, respectively. Stimulations of the G i -coupled α 2A -adrenergic receptor, fMet-Leu-Phe receptor, prostaglandin EP3α receptor, and G s -coupled β 2 -adrenergic receptor did not activate AMPKα1. AMPKα1 thus is activated specifically by stimulation of G q -coupled receptors. G q -coupled receptors transmit the signal for GLUT4 translocation and glucose uptake through an insulin-independent pathway. However, direct activation of AMPKα1 with treatment of 5-aminoimidazole-4-carboxamide-1-β- d -ribofuranoside did not trigger GLUT4 translocation nor stimulate glucose uptake in our cells. Thus, activation of AMPKα1 via G q is not sufficient to trigger GLUT4 translocation or stimulate glucose uptake.