Arachidonic acid metabolites do not mediate modulation of neurotransmitter release by adenosine in rat hippocampus or striatum.
The possible involvement of arachidonic acid metabolites as mediators of the modulation of neurotransmitter release by adenosine, acetylcholine, and GABA was examined in brain slices of rat hippocampus and striatum. The synaptic modulatory effects of these 3 agents on excitatory transmission in the CA1 region of hippocampus were completely unaffected by a phospholipase inhibitor (p-bromophenacyl bromide, BPB; 10-50 microM), a lipoxygenase inhibitor (nordihydroguaiaretic acid; 5-50 microM), the cyclooxygenase inhibitor indomethacin (10-20 microM), and a cyclooxygenase/lipoxygenase inhibitor (U53059; 5-10 microM). BPB was also found to be ineffective in altering the modulation of transmission by adenosine in the perforant path, and the adenosine inhibition of electrically stimulated release of endogenous dopamine from striatal slices. Arachidonic acid itself also had no effect on synaptic transmission. While these experiments do not rule out such a role for arachidonic acid or its metabolites in mammalian brain, they suggest that in a number of systems the inhibition of transmitter release must occur through an entirely independent mechanism.
Dunwiddie
T V
TV
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80206.
Taylor
M
M
Cass
W A
WA
Fitzpatrick
F A
FA
Zahniser
N R
NR
D000098:Acetophenones / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D015290:Second Messenger Systems / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology
D000098:Acetophenones; D001095:Arachidonic Acids; D016859:Lipoxygenase Inhibitors; D018377:Neurotransmitter Agents; D013844:Thiazoles; D016718:Arachidonic Acid; D009637:Masoprocol; D002217:Carbachol; D010740:Phospholipases; D001418:Baclofen; D000241:Adenosine; C035025:itazigrel; C006821:4-bromophenacyl bromide; D007213:Indomethacin