Pertussis toxin prevents presynaptic inhibition by kainate receptors of rat hippocampal [(3)H]GABA release.
Kainate receptors are ionotropic receptors, also reported to couple to G(i)/G(o) proteins, increasing neuronal excitability through disinhibition of neuronal circuits. We directly tested in hippocampal synaptosomes if kainate receptor-mediated inhibition of GABA release involved a metabotropic action. The kainate analogue, domoate (3 microM), inhibited by 24% [(3)H]GABA-evoked release, an effect reduced by 76% in synaptosomes pre-treated with pertussis toxin. Protein kinase C inhibition attenuated by 82% domoate-induced inhibition of GABA release whereas protein kinase C activation did not change kainate receptor binding. Thus, domoate inhibition of GABA release recruits G(i)/G(o) proteins and a protein kinase C pathway.
Cunha
R A
RA
Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal. racunha@neurociencias.pt
Malva
J O
JO
Ribeiro
J A
JA
D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D017729:Presynaptic Terminals / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000378:metabolism / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019204:GTP-Binding Proteins; D007608:Kainic Acid; D037342:Pertussis Toxin; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; D017661:Receptors, Presynaptic; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; C012301:domoic acid