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  • Title: Cerebral GABA receptors.
    Author: Kuriyama K.
    Journal: Alcohol Alcohol Suppl; 1994; 2():181-6. PubMed ID: 8974333.
    Abstract:
    GABA (gamma-aminobutyric acid) receptors in the brain have been classified into GABAA and GABAB types. The GABAA receptor is an ionotropic type that forms the GABA-gated Cl- channel. The structure of GABAA receptor has been intensively analyzed and found to consist of several subunits and the combination of these subunits is heterogeneous. Therefore, it is likely that multiple GABAA receptors are present and exert various inhibitory actions in the brain. On the other hand, the GABAB receptor, a metabotropic type, inhibits cAMP formation as well as inositol phosphates turnover. The inhibition of adenylyl cyclase activity is mediated by GTP-binding protein such as Gi and/or Go which is coupled with GABAB receptor. Studies of the purified GABAB receptor obtained by baclofen-affinity and immunoaffinity column chromatographic procedures have indicated that this receptor protein is approximately 80 kDa in molecular weight and heterogeneous as determined by SDS-polyacrylamide gel electrophoresis. Alcohol induces the activation of GABA-gated Cl- channel but this activation is found to be diminished following the establishment of alcohol dependence. Furthermore, alcohol dependence induces the increase of GABAB receptor binding, while suppressing the functional coupling between GABAB receptor and adenylyl cyclase, possibly altering the function of Gi/Go type of GTP-binding protein which is coupled to GABAB receptor in the brain. The pathophysiological significance of these changes in the establishment of alcohol dependence and/or alcohol withdrawal syndrome is also briefly discussed.
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