Regional effects of pertussis toxin in vivo and in vitro on GABAB receptor binding in rat brain

Abstract Agonist binding to GABA B receptors modulates the activity of the guanine nucleotide binding proteins, Go and Gi. These G proteins are ADP-ribosylated by pertussis toxin and this prevents them from coupling to the GABA B receptor resulting in a reduction in high-affinity GABA B binding. GTP, which binds to a different site on the G protein α subunit, also reduces the affinity of the receptor for the G protein, and this can be used as a “marker” for G protein-GABA B receptor linkage. We have examined GABA B binding site distribution in rat brain after unilateral intrahippocampal pertussis toxin injection in vivo , and after incubating brain slices in pertussis toxin in vitro , using the technique of receptor autoradiography. The effect of pertussis toxin was compared with that of GTPγS on GABA B binding. Intrahippocampal pertussis toxin administration reduced GABA B but not GABA A receptor binding and the effects appeared to be limited by pertussis toxin diffusion. More widespread reductions in GABA B binding were seen after incubation of brain slices in vitro but the extent varied in different brain regions. No reduction was detected in the corpus striatum. GABA B binding was also reduced in membranes prepared from cerebral cortex, hippocampus and cerebellum but there was no sigificant reduction in the corpus striatum after pertussis toxin treatment. GTPγS reduced GABA B binding to a similar extent in all areas studied irrespective of their sensitivity to pertussis toxin suggesting that while GABA B binding sites are linked to G proteins throughout the rat brain, those in the corpus striatum may be predominantly pertussis toxin insensitive.