2-Amino-3-phosphonopropionate blocks the induction and maintenance of long-term potentiation in rat hippocampal slices.
Rat hippocampal slices were used to examine the effects of 2-amino-3-phosphonopropionate (AP3), an inhibitor of phosphatidylinositol (PI) turnover linked to metabotropic quisqualate receptors, on the development and maintenance of long-term potentiation (LTP) in area CA1. When perfused for 5 min prior to tetanization at concentrations of 100-1000 microM, D,L-AP3 had no effect on baseline synaptic transmission but blocked posttetanic potentiation (PTP) and the induction of LTP. Unlike the N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovalerate (AP5) and MK-801, AP3 eliminated the late phase of LTP when applied immediately after tetanization. These data support the hypothesis that PI turnover is a factor in the expression and maintenance of LTP.
Department of Psychiatry, Washington University Medical School, St. Louis, MO 63110.
Y
Y
Izumi
D B
DB
Clifford
C F
CF
Zorumski
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D005971:Glutamates; C000211:2-amino-3-phosphonopropionic acid; D018698:Glutamic Acid; D016318:Quisqualic Acid; D000409:Alanine