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NMDA Receptor-Stimulated Release of Arachidonic Acid: Mechanisms for the Bazan Effect

  • Lloyd A. Horrocks
  • Akhlaq A. Farooqui

Summary

Excitatory amino acids, acting through the NMDA type of glutamate receptors, cause the release of arachidonic acid. Long-term potentiation in the hippocampus causes this release, part of the normal physiological process essential for memory. Overactivation of these receptors occurs in stroke, epilepsy, and other neurodegenerative diseases.

The activation of pnospnoiipases and lipases, and increased membrane phospholipid hydrolysis with accumulation of free fatty acids (FFAs) and diacylglycerol, is harmful to neurons in three ways: (1) Loss of essential phospholipids from the membrane structure, with accumulation of FFAs, diacylglycerols, lysophospholipids, and platelet activating factor (PAF). This is the Bazan effect (Bazan, 1970). FFAs, diacylglycerols, and lysophospholipids have a detergent-like effect on neuronal membranes. They can uncouple oxidative phosphorylation and produce changes in membrane permeability by regulating ion channels (Keyser and Alger, 1990). PAF is proaggregatory and hemostatic; it may cause adhesion and activation of leukocytes and hence produce an inflammatory reaction at the blood-endothelial cell interface and open Ca2+ channels on presynaptic sites, causing increased release of glutamate (Clark et al., 1992). (2) The accumulation of FFAs can trigger an uncontrolled ‘arachidonic acid cascade’. This includes the synthesis of prostaglandins, leukotrienes, and thromboxanes. An uncontrolled arachidonic acid cascade sets the stage for the increased production of free radicals and hence for lipid peroxidation and oxidative damage to membrane proteins. (3) Finally, calcium influx through increased phospholipid degradation may lead to sustained activation of protein kinase C and its translocation from cytosol to plasma membrane (Asaoka et al., 1992; Melloni et al., 1985; Nishizuka, 1992). The stimulation and translocation of protein kinase C may also be involved in neurodegeneration (Asaoka et al., 1992; Nishizuka, 1992).

Keywords

Nitric Oxide Lipase Activity Cerebellar Granule Cell Alzheimer Disease Patient Arachidonic Acid Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Lloyd A. Horrocks
    • 1
  • Akhlaq A. Farooqui
    • 1
  1. 1.Department of Medical BiochemistryThe Ohio State UniversityColumbusUSA

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