Through its activation by GPCRs, Gαo is involved as a modulator or transducer in several transmembrane signaling pathways.10,12,13 Gαo also mediates the widespread presynaptic autoinhibitory effect of many neurotransmitters (via α2 adrenoreceptors, M2/M4 muscarinic, μ/δ opioid, GABAB, adenosine A1, or endocannabinoid CB1 receptors) through a reduction of sensitivity to membrane depolarization and a direct inhibitory effect on the vesicle fusion process.14 Furthermore, Gαo indirectly activates G protein–coupled inwardly rectifying K+ channels that mediate neuronal excitability through a slower self-inhibitory postsynaptic potential.15
