The present work was aimed at studying the release of arachidonic acid and formation of lipoxygenase metabolites in rat brain slices maintained in vitro, as well as exploring possible physiological roles for them in the mammalian central nervous system. A particularly active 12-(S)-lipoxygenase activity was found, which could be stimulated by various stimuli including the neurotransmitters norepinephrine and glutamate. Activation of $ alpha$-adrenergic and N-methyl- scD-aspartate (NMDA) receptor subtypes appear responsible for the effect observed in each case. Arachidonic acid on the other hand was found to have profound effects on synaptic transmission, inducing a long-lasting potentiation which appears dependent on the formation of lipoxygenase metabolites. In return, pharmacological conditions which can potentially lead to long-term potentiation (LTP) of synaptic transmission and for most of them activate NMDA receptors also induced arachidonic acid release. As these observations suggest, it is proposed that arachidonic acid and its lipoxygenase metabolites belong to a new group of messengers in the nervous system possibly acting as modulator of synaptic transmission both intra- and transcellularly. This new class of messengers constitutes an essential component of the molecular machinery involved in synaptic plasticity.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.70251 |
| Date | January 1992 |
| Creators | Pellerin, Luc |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001265152, proquestno: AAINN74464, Theses scanned by UMI/ProQuest. |
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