Different routes of Ca2+ influx in NMDA-mediated generation of nitric oxide and arachidonic acid.
Nitric oxide and arachidonic acid act as inter- and intracellular messengers in the central nervous system. It is well known that the NMDA-mediated generation of nitric oxide and arachidonic acid is dependent on extracellular Ca2+. However, the role of voltage-dependent calcium channels (VDCCs) in this regard is poorly understood. We report here that NMDA-mediated nitric oxide production in striatal neuron cultures is blocked (80%) by the L-type VDCC antagonist nifedipine, but not by omega-conotoxin or omega-agatoxin IVA, antagonists of the N- and P-type VDCCs respectively. By contrast, none of the VDCC antagonists inhibited the NMDA-mediated release of arachidonic acid. These data indicate that permeation through different Ca2+ channels is responsible for the production of arachidonic acid and nitric oxide in striatal neurons.
Rodriguez-Alvarez
J
J
CNRS, UPR 9023, CCIPE, Montpellier, France.
Lafon-Cazal
M
M
Blanco
I
I
Bockaert
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000096:biosynthesis*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020746:Calcium Channels, L-Type; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D005333:Fetus; D007700:Kinetics; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D010455:Peptides / Q000494:pharmacology; D013111:Spider Venoms / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D016718:Arachidonic Acid; D009569:Nitric Oxide; D016202:N-Methylaspartate; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020866:omega-Conotoxin GVIA; D006152:Cyclic GMP; D009543:Nifedipine