The Role of G Proteins in the Pathophysiology and Treatment of Affective Disorders

Abstract

Guanosine triphosphate (GTP)-binding proteins (G proteins) have been thought of as modulators that multiply signal information from receptors to effectors. G proteins related to membrane signaling have a heterotrimetric structure (α, β, and γ), and the α subunit has a GTP-binding site involved in GTPase activity hydrolyzing GTP to guanosine diphosphate (GDP). Therefore, the G proteins comprise a unique family of protein molecules implicated in the mechanisms switching signal transduction on and off (Simon et al. 1991). Manic-depressive illness is characterized by two phases, the manic and the depressive states, and generally is considered to be in remission in the period between episodes. From its clinical characteristics, it is conceivable that there is some difficulty in emotional adjustment involving the switching mechanisms that accelerate or diminish neurotransmission in the brain. Hence, one might assume that there is a close relationship between G protein as the protein molecule in the on-off signal switching and manic-depressive illness (Fig. 1). Since the amine hypothesis of manic-depressive illness was proposed, various hypotheses concerning the pathophysiology of this disorder have been discussed, along with the complexity of interactions among multiple neural trans-mission systems, which contrasts with the increase or decrease in single neurotransmitters such as occurs with noradrenaline and serotonin. One of the neurological bases of signal interaction is that different receptors are coupled with the same G protein.