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AgRP neurons of the ARC express GLP1 receptors that couple to Gs proteins and activate the membranous adenylate cyclase (AC). PKA is activated downstream of cAMP, which increases calcium entry through Cav1.4 channels that eventually activate SK3 potassium channels and shut down neuronal activity.139As a result, these GABA neurons no longer inhibit MC4R neurons, and hunger decreases. Setmelanotide activates MC4R neurons via a G protein-independent direct interaction with Kir7.1 potassium channels.140

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