GABA와 Benzodiazepine 수용체 및 그 기능 = GABA, Benzodiazepine Receptors and Their Functions

다국어 초록 (Multilingual Abstract)

GABA is ubiquitously distributed throughout the CNS. It is probably the major central inhibitory aminoacid neurotransmitter which hyperpolarizes the postsynapic neurons and inhibits the release of neurotransmitters. Generally inhibition of GABA activity causes excitation leading to anxiety and convulsions, whereas activation of its activity causes antiexpressive. anticonvulsive activity and sedation.
The GABA receptors have been divided into two distinct groups named GABA(A) and GABA(B) receptors by their pharmacological and physiological properties. GABA(A) receptors are coupled with Bz binding site and that in conjunction with a CI­ channel they form a supramolecular receptor complex which mediates rapid increasing of CI­ influx into postsynaptic neurons. thus contributing to the prompt inhibition of cellular excitability.
On the contrary, the GABA(B) receptor does not contain an integral ion channel and is responsible for slow responses through receptor-G protein-effector complexes. GABA(B) receptors appear to be localized on presynaptic nerve terminals and stimulation of presynaptic GABA(B) receptors reduced Ca²+ influx, resulting in decreased release of neurotransmitters. Stimulation of presynaptic GABA(B) receptors increases K efflux, resulting in inhibition of cell firing.
A division of function among the two types of GABA receptors appears to exist : GABA(A) receptor complex mediates anxiety, anticonvulsive activity and feeding, GABA(B) receptors, on the other hand, are involved in depression and analgesia. In those cases where GABA(A) and GABA(B) receptors mediate similar functions (e.g., cardiovascular regulation), they do so by affecting different transmitter systems and cellular mechanisms. The putative involvement of GABA(A) and GABA(B) receptors in various behavioral and physiological effects is summarized in Table 3.
There are two types of Bz receptors in brain which are central and peripheral type Bz receptors. Central Bz receptors are in many regions of the brain, coupled with the receptors for GABA and they mediate the acute actions of Bz in CNS. Although there is general acceptance that Bz evert their major actions via the GABA(A) receptor, more recent studies suggest that other systems may be involved.
In addition, endogenous anxiogenic ligands that interact with Bz receptors in several ways have been discovered, which of these,β-carbolines and DBI may produce anxiety and convulsion in human,
The recent investigation of endogenous ligands and specific receptor agonist or antagonist and inverse agonist provide important new conceptual tools for the studies of anxiety and depression mechanisms. It is expected that a better understanding of GABA and Bz receptors will eventually help to demonstrate the biology of anxiety and depression.