All melanocortin receptors are class A G-protein-coupled receptors signalling principally through Gs and adenylyl cyclase to raise intracellular cAMP, and MC4R is the subtype whose ligand-bound active-state architecture is best resolved, including a 2021 cryo-EM series that captured bremelanotide bound to full-length MC4R in complex with heterotrimeric Gs
With regards to symptom improvement, while there was a substantial reduction in IBS-SSS (as well as GSRS sub scores for diarrhea, bloating and pain), change in IBS-SSS was not correlated with changes in GLP-1
Reference: Alpert A J, Gilbert H F
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