G-Protein Linked Effect of Pasteurella Multocida Toxin on GABA Outflow from Neocortical Synaptosomes

Pasteurella Multocida Toxin (PMT) stimulates diverse cellular signal transduction pathways by activating heterotrimeric G proteins through deamidation of a a-subunit glutamine residue of the G-protein. Since mammalian cells are able to take up PMT probably by receptor-mediated endocytosis, the question was raised whether PMT is capable of modulating γ-aminobutyric acid (GABA) outflow from neocortical synaptosomes of the rat in vitro. In our experiments PMT did not modify basal GABA outflow. However, GABA release induced by potassium ions was significantly reduced. Here the toxin effect was not modulated by the GABAB-receptor agonist baclofen. These results let us to suggest that PMT activates G-proteins of the inhibitory metabotropic GABAB autoreceptor on GABAergic nerve terminals.