Postsynaptic action of endogenous GABA released by nipecotic acid in the hippocampus.
Intracellular and whole-cell recording from CA1 pyramidal cells and dentate granule cells was used to study the release of endogenous GABA by nipecotic acid. Local application of nipecotic acid produced responses that could be entirely blocked by a combination of the GABAA receptor antagonist picrotoxin and the GABAB receptor antagonist CGP 35348. These responses were due to the heteroexchange release of endogenous GABA because they were blocked by low Na+ which blocks the GABA transporter and by SKF 89976 which is a competitive antagonist of the GABA transporter. Local application of nipecotic acid could, depending on the location, evoke pure GABAA or pure GABAB responses supporting proposals that GABAA and GABAB receptors can be segregated at separate inhibitory synapses.
Solís
J M
JM
Department of Pharmacology, University of Califoria, San Francisco 91413-0450.
Nicoll
R A
RA
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004566:Electrodes; D058787:GABA-A Receptor Antagonists; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D009557:Nipecotic Acids / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D011392:Proline; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C030278:nipecotic acid; C066430:CGP 35348; C010983:homoproline