GABA preincubation of rat brain sections increases [ 3H]GABA binding to the GABA A receptor and compromises the modulatory interactions

Abstract

Receptor autoradiography has been employed to investigate the effect of γ-aminobutyric acid (GABA) preincubation on the interaction of the GABA A receptor with its ligands. [ 3H]GABA (50 nM) binding to the GABA A receptors is increased by 60% compared to control sections after GABA (100 μM) preincubation. Receptor autoradiography shows that the increase is more pronounced in certain brain areas. The allosteric interactions between the GABA and benzodiazepine recognition sites were also examined. An increase in [ 3H]GABA (50 nM) binding to rat brain sections by co-incubation with the benzodiazepine, flunitrazepam (FNZ) has been observed autoradiographically. This effect has been quantitated in several brain regions; the overall brain increase in [ 3H]GABA binding induced by 1 μM FNZ was 20%. The increase in [ 3H]FNZ (1 nM) binding by co-incubation with GABA has also been observed autoradiographically, and the effect quantitated in four brain regions. The overall brain increase in [ 3H]FNZ binding induced by 100 μM GABA was 34%. After GABA preincubation these allosteric responses are significantly reduced in size. The increase in the [ 3H]GABA A binding as a consequence of GABA preincubation appears to reflect an increase in receptor affinity for [ 3H]GABA with no significant change in the maximum number of binding sites. We suggest that GABA preincubation converts the GABA A receptor to a higher affinity desensitised receptor conformation.