Modulation of DL-. alpha. -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/quisqualate receptors by phospholipase A sub 2 : A necessary step in long-term potentiation

Journal Article · Fri Mar 01 00:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.5.1893· OSTI ID:6144644

Massicotte, G; Baudry, M ^[1]; Vanderklish, P; Lynch, G ^[2]

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1. Univ. of Southern California, Los Angeles (United States)
2. Univ. of California, Irvine (United States)

The effects of kainate (KA)-induced epileptic seizures on the binding properites of hippocampal glutamate receptors, on the modulation of DL-{alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/quisqualate receptor by phospholipase A{sub 2} (PLA{sub 2}), and on the formation of long-term potentiation (LTP) were studied in hippocampal membranes and hippocampal slices. Systemic administration of KA produced specific changes in the binding properties of the AMPA/quisqualate receptors and its regulation. Whereas the binding of various ligands to the N-methyl-D-aspartate receptors was not modified by KA treatment, there was a singificant decrease in the maximal number of binding sites for ({sup 3}H)AMPA. The loss of LTP was not due to changes in postsynaptic responses elicited by the bursts that trigger the potentiation effect, thus suggesting that KA treatment disrupts processes that follow N-methyl-D-aspartate receptor activation. Systemic administration of KA was associated with calpain activation as the amount of spectrin breakdown products was increased severalfold in hippocampus but not in cerebellum. Pretreatment of telencephalic membranes with calpain greatly reduced the PLA{sub 2}-induced increase in ({sup 3}H)AMPA binding. The results provide evidence in favor of an essential role of PLA{sub 2} in the development of LTP and suggest that the order of activation of different calcium-dependent processes is critical for producing the final changes underlying LTP.

• OSTI ID: 6144644
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 88:5; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
EPILEPSY
PATHOGENESIS
LIPASES
BIOLOGICAL EFFECTS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
GLUTAMIC ACID
HIPPOCAMPUS
PROPIONIC ACID
TRITIUM COMPOUNDS
AMINO ACIDS
BODY
BRAIN
CARBOXYLESTERASES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
DISEASES
ENZYMES
ESTERASES
HYDROGEN COMPOUNDS
HYDROLASES
KINETICS
MEMBRANE PROTEINS
MONOCARBOXYLIC ACIDS
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
550201* - Biochemistry- Tracer Techniques