GABA와 Benzodiazepine 수용체 및 그 기능

GABA, Benzodiazepine Receptors and Their Functions

GABA is ubiquitously distributed throughtout the CNS. It is probably the m ajor central inhibitory am inoacid neurotransm itter which hyperpolarizes the postsynapic neurons and inhibits the release o f neurotransm itters. G enerally inhibition o f GABA activity causes excitation leading to anxiety and convulsions, whereas activation of its activity causes antidepressive, anticonvulsive activity and sedation. The GABA receptors have been divided into two distinct groups nam ed GABAa and GABAb receptors by their pharm acological and physiological properties. GABAa receptors are coupled with Bz binding site and that in conjunction with a C l- channel they form a supram olecular receptor com plex which m ediates rapid increasing o f C厂 influx into postsynaptic neurons, thus contributing to the prom pt inhibition of cellular excitability. O n the contrary, the GABAb receptor does not contain an integral ion channel and is responsible for slow responses through receptor-G protein-effector complexes, GABAb receptors appear to be localized on presynaptic nerve term inals and stim ulation o f presynaptic GABAb receptors reduced C a2+ influx, resulting in decreased release of neurotransmitters. Stimulation of presynaptic GABAb receptors increases K+ efflux, resulting in inhibition of cell firing. A division of function am ong the two types of GABA rceptors appears to e x ist; GABAa receptor complex mediates anxiety, anticonvulsive acitivty and feeding, GABAb receptors, on the other hand, are involved in depression and analgesia. In those cases where G A^BAa and GABAb receptors m ediate similar functions (e.g., cardiovascular regulation), they do so by affecting different transm itter systems and cellular mechanisms. The putative involvememt of GABAa and GABAb receptors in various behavioral and physiological effects is sum m arized in Table 3. T here 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 exert their m ajor actions via the GABAa receptors, m ore recent studies suggest that other systems may be involved. In addition, endogenous anxiogenic ligands that interact with Bz recrptors in several ways have been discovered, which of these, P-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 im portant 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 dem onstrate the biology of anxiety and depression.