GABA: homeostatic and pharmacological aspects.
The central nervous system (CNS) operates by a fine-tuned balance between excitatory and inhibitory signalling. In this context, the inhibitory neurotransmission may be of particular interest as it has been suggested that such neuronal pathways may constitute 'command pathways' and the principle of 'dis-inhibition' leading ultimately to excitation may play a fundamental role (Roberts, E. (1974). Adv. Neurol., 5: 127-143). The neurotransmitter responsible for this signalling is gamma-aminobutyrate (GABA) which was first discovered in the CNS as a curious amino acid (Roberts, E., Frankel, S. (1950). J. Biol. Chem., 187: 55-63) and later proposed as an inhibitory neurotransmitter (Curtis, D.R., Watkins, J.C. (1960). J. Neurochem., 6: 117-141; Krnjevic, K., Schwartz, S. (1967). Exp. Brain Res., 3: 320-336). The present review will describe aspects of GABAergic neurotransmission related to homeostatic mechanisms such as biosynthesis, metabolism, release and inactivation. Additionally, pharmacological and therapeutic aspects of this will be discussed.
Schousboe
Arne
A
Department of Pharmacology and Pharmacotherapy, The Faculty of Pharmaceutical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. as@dfuni.dk
Waagepetersen
Helle S
HS
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D033921:Vesicular Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000737:chemistry / Q000378:metabolism*
D018079:Receptors, GABA; D033921:Vesicular Transport Proteins; D005680:gamma-Aminobutyric Acid