G proteins: implications for psychiatry.
There is mounting evidence that a family of guanosine triphosphate binding proteins (G proteins) play an obligatory role in the transduction of a vast array of extracellular, receptor-detected signals across cell membranes to intracellular effectors. The author reviews the literature dealing with G protein coupling to second messenger generation, the role of G proteins in regulating both the convergence and divergence of neurotransmitter action in the CNS, and the involvement of G proteins in a variety of clinical conditions, with an emphasis on psychiatric conditions and their treatments. G proteins from the basis of signal integration in the CNS, endowing the neuron with a large degree of functional diversity. Abnormalities in the function and/or expression of G proteins have been implicated in a variety of pathophysiologic states, and a number of currently available psychotropic drugs affect G proteins. The understanding of the mechanisms by which G proteins modulate neuronal activity may be one of the keys to understanding the functioning and the complexities of the nervous system. Given their widespread, critical roles in the regulation of neuronal function, it seems likely that G proteins are involved in the pathophysiology of various major psychiatric illnesses. The development of novel, site-specific drugs with primary G protein targets remains an exciting prospect for the future.
Manji
H K
HK
Section on Clinical Pharmacology, NIMH, Bethesda, MD 20892.
D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism / Q000503:physiopathology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology
D018377:Neurotransmitter Agents; D019204:GTP-Binding Proteins