The AMP-activated protein kinase (AMPK) functions as a metabolic sensor that monitors cellular AMP and ATP levels. Platelet-activating factor (PAF) activates endogeneous AMPK alpha 1 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 AMPK alpha 1 in cells expressing the G(q)-coupled alpha(1b)-adrenergic receptor and bradykinin receptor, respectively. Stimulations of the G(i)-coupled alpha(2A)-adrenergic receptor, fMet-Leu-Phe receptor, prostaglandin EP3 alpha receptor, and G(s)-coupled beta(2)-adrenergic receptor did not activate AMPK alpha 1. AMPK alpha 1 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 AMPK alpha 1 with treatment of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside did not trigger GLUT4 translocation nor stimulate glucose uptake in our cells. Thus, activation of AMPK alpha 1 via G(q) is not sufficient to trigger GLUT4 translocation or stimulate glucose uptake.