Presynaptic inhibitory effect of baclofen on hippocampal inhibitory synaptic transmission involves a pertussis toxin-sensitive G-protein.
The involvement of a pertussis toxin (PTX)-sensitive G-protein in the activation of presynaptic GABAB receptor is controversial. In the present study, we reinvestigated the problem using intracellular recordings from CA1 neurons in rat hippocampus slices. We showed that the presynaptic inhibitory effect of baclofen is mediated differently at excitatory and inhibitory synapses. Excitatory (e.p.s.p.) and inhibitory (i.p.s.p.) postsynaptic potentials were strongly antagonized by baclofen in control rats. Three days after administration of PTX into the stratum radiatum of the hippocampus, the inhibitory effect of baclofen on i.p.s.p. was antagonized. In contrast, the inhibitory effect on e.p.s.p. was partly maintained. These results suggest that different sub-types of GABAB receptors exist on nerve terminals with different transduction mechanisms. GABAB receptors located on GABAergic inhibitory terminals are linked to a PTX-sensitive G-protein, whereas those located on excitatory terminals could consist of a PTX-sensitive type and a PTX-insensitive type. In addition, we showed that part of the inhibitory effect of baclofen at excitatory synapses is independent of omega-conotoxin (omega-CgTx)-sensitive N-type Ca2+ channels.
Laboratoire de Physiopharmacologie du Système Nerveux, INSERM U 161, Paris, France.
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D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D011963:Receptors, GABA-A; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D001418:Baclofen