The role of N-methyl-D-aspartate receptors and nitric oxide in cochlear dopamine release.
Dopamine (DA) released from lateral olivocochlear (LOC) terminals may have a neuroprotective effect in the cochlea. To explore the role of N-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) in the modulation of a cochlear DA release, we measured the release of [3H]DA from isolated mouse cochlea in response to the application of NMDA. NMDA at 100 muM significantly increased the electrical-field stimulation-evoked and resting release of DA from the cochlea. The NO donor sodium nitroprusside enhanced the basal outflow of DA but failed to influence the evoked release. The administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) alone was ineffective, but it significantly inhibited the initial phase of the NMDA-induced elevation of DA outflow, which suggested the role of NO in the NMDA-induced DA release. The DA uptake inhibitor nomifensine increased the electrically evoked release of DA. Nomifensine failed to change the effect of NMDA on the resting or electrically-evoked DA release, which suggested that the uptake mechanism does not play a role in NMDA-evoked and NO-mediated DA release. In summary, we provide evidence that NO can modulate the release of DA from the cochlea following NMDA receptor activation, but does not affect the uptake of DA.
Halmos
G
G
Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, Budapest, Hungary.
Horváth
T
T
Polony
G
G
Fekete
A
A
Kittel
A
A
Vizi
E S
ES
van der Laan
B F A M
BF
Zelles
T
T
Lendvai
B
B
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D003051:Cochlea / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D009599:Nitroprusside; D009569:Nitric Oxide; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine