G-proteins (guanine nucleotide-binding proteins) are membrane-attached proteins composed of three subunits, alpha, beta, and gamma. They transduce signals from G-protein coupled receptors (GPCRs) to target effector proteins. The agonistactivated receptor induces a conformational change in the G-protein trimer so that the alpha-subunit binds GTP in exchange for GDP and alpha-GTP, and betagamma-subunits separate to interact with the target effector. Effector-interaction is terminated by the alpha-subunit GTPase activity, whereby bound GTP is hydrolyzed to GDP. This is accelerated in situ by RGS proteins, acting as GTPase-activating proteins (GAPs). Galpha-GDP and Gbetagamma then reassociate to form the Galphabetagamma trimer. G-proteins primarily involved in the modulation of neurotransmitter release are G(o), G(q) and G(s). G(o) mediates the widespread presynaptic auto-inhibitory effect of many neurotransmitters (e.g., via M2/M4 muscarinic receptors, alpha(2) adrenoreceptors, micro/delta opioid receptors, GABAB receptors). The G(o) betagamma-subunit acts in two ways: first, and most ubiquitously, by direct binding to CaV2 Ca(2+) channels, resulting in a reduced sensitivity to membrane depolarization and reduced Ca(2+) influx during the terminal action potential; and second, through a direct inhibitory effect on the transmitter release machinery, by binding to proteins of the SNARE complex. G(s) and G(q) are mainly responsible for receptor-mediated facilitatory effects, through activation of target enzymes (adenylate cyclase, AC and phospholipase-C, PLC respectively) by the GTP-bound alpha-subunits.