G蛋白與精神疾病

G Protein and Mental Disorders

陳益乾(Yi-Chyan Chen)

《Journal of Medical Sciences》 17卷2期 (1996/10) Pp. 61-76

摘要

G蛋白是一群與鳥核苷結合之蛋白質，由α、β、γ三個次單元組合而成之異形三聚體，存在於細胞膜上，負責傳遞來自細胞表面的生物化學訊息。依其多樣化的次單元結構，可將訊息整合轉換，改變離子通道及酶之活性，進而調節第二信使之傳導功能，再經由蛋白激酶將訊息予以修飾，產生精緻專一的生理反應；而G蛋白是訊息傳遞過程中之調控樞紐，它可整合來自不同神經介質及不同受體之刺激，更可調節不同傳導路徑酶之活性，彼此相互連繫，相輔相成，構成一精密之神經網路。過去生物精神醫學之研究，著重於探討神經介質代謝及受體功能異常與精神疾病之關係，但難有一致之結果。本文回顧相關文獻，分析G蛋白調節機制異常與精神藥物間之關係，期能對精神疾病在生物精神醫學上提出另一種不同的假說。

關鍵字

G蛋白 ； 神經介質 ； 受體 ； 訊息轉換 ； 受動器 ； 精神疾病 ； 精神藥物

並列摘要

G proteins are a family of guanine nucleotide-binding proteins which consist of an α-subunit and inseparable β, γ-subunit complex. The heterotrimeric G protein play a pivotal role in postreceptor information transduction that carry information received at cellular surface to cellular effector systems. G protein-mediated signal transduction is initiated by ligand-bound receptor. This activated receptor is able to interact with G protein and promotes the exchange of GDP, bound to the α-subunit, for GTP and subsequent dissociation of α-GTP complex from βγcomplex heterodimer. Gα-GTP is able to bind and regulate the appropriate effector systems. The mechanism is inactivated by hydrolysis of α-GDP via GTPase. Then α subunit reassociates with the βγcomplex and the system returns to its resting state. These G-protein-mediated cascades regulate both convergence and divergence of and neural activity. G-proteins form the basis of signal integration in CNS, endowing the neuron with a large degree of functional diversity. Abnormalities in the function and expression of G proteins have been implicated in a variety of pathophysiologic states and a number of available psychotropic drugs affect G proteins. To understand the mechanism of G protein-modulating neuronal activity would help us to understand the complexities and function of the nervous system. In this article, the author will discuss how the G protein to influence the pathophysiology of major mental disorders.

並列關鍵字

G protein ； neurotransmitter ； recetpor ； signal transduction ； effector ； mental disorder ； psychotropic drug