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The most studied effector is the adenylyl cyclase (ACase) and investigations on OR coupling demonstrated that stimulation of MOR, DOR, and KOR in cellular models or ex vivo inhibited ACase mainly via G i/o proteins (Dhawan et al., 2+ channels or activation of potassium channels such as GIRK (G protein-coupled inwardly rectifying K + channels) (Law et al., 2000)