Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

Several lines of evidence support the presence of a G protein-coupled benzodiazepine receptor (G-BZR) which is negatively linked to the adenylyl cyclase-cAMP pathway in the brain. For example: 1)The binding affinity of the non-selective BZ agonist, diazepam, is decreased significantly in the presence of guanosine triphosphate. 2)Diazepam and Ro5-4864, a peripheral-type BZ agonist, cause a concentration-dependent inhibition of forskolin-stimulated adenylyl cyclase (AC)activity in the striatum. 3)Pretreatment of striatal slices with pertussis toxin blocks the effect of BZs on AC activity, indicating involvement of an inhibitory G protein (Gi). 4)Preincubation of striatal membranes with diazepam stimulates [alpha-32P]GTP binding to a 40 kDa protein, presumably Gi. 5) The central-type BZ receptor antagonist, flumazenil, does not affect BZ-induced suppression of AC, which shows that the BZ-GABAa-ionophore complex is not involved. 6) In contrast, the peripheral (mitochondrial)-type BZ receptor ligand, PK 11195, blocks G-BZR-mediated inhibition of AC by BZs, suggesting that the G-BZR is a plasma membrane -localized subtype of the peripheral-type BZ receptor. Further studies are required to determine the role of the G-BZR in the psychopharmacological spectrum of effects attributed to the BZs and endogenous activators of BZ receptors.

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Poster Number PAniles0559
Keywords: diazepam, ro5-4864, pk 11195, adenylyl cyclase, pertussis toxin