Arachidonic acid metabolites as mediators of synaptic modulation.
The neurotransmitters histamine, dopamine and the peptide Phe-Met-Arg-Phe-NH2 (FMRFa) cause presynaptic inhibition in the nervous system of the marine mollusk Aplysia Californica by combined down-modulation of a Ca++ conductance and up-modulation of a K+ conductance. The action of FMRFa on the S-type K+ channels of Aplysia sensory neurons is mediated by a metabolite of the 12-lipoxygenase pathway of arachidonic acid, possibly 12-HPETE. A Pertussis toxin-sensitive GTP binding protein couples FMRFa receptor to the activation of the arachidonic cascade. Once produced, 12-HPETE does not require ATP- or GTP-dependent processes to act on the K+ channels, but it may directly modulate the channel via an external membrane receptor. Based on this observation, a role for eicosanoids as possible intercellular messengers in the C.N.S. is discussed.
Volterra
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Department of Pharmacology, Howard Hughes Medical Institute, Columbia University, New York, N.Y. 10002.
D000818:Animals; D001048:Aplysia / Q000502:physiology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D001095:Arachidonic Acids; D016718:Arachidonic Acid