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.