The CaM-kinase II inhibitor KN-62 blocks NMDA but not kainate stimulation of NO synthesis.
We have studied the effect of CaM-kinase II inhibition induced by KN-62 on NO synthesis mediated by the activation of NMDA and kainate receptors in striatal neurones. KN-62 partially inhibited NMDA-mediated NO synthesis but the effect of kainate on NO production was unaffected by the specific CaM-kinase II inhibitor. Ionomycin-induced cGMP production and the NMDA-mediated superoxide generation by nNOS were also inhibited by KN-62. Since we determined the NO synthesis via its ability to increase intracellular cGMP, we checked that the kinase inhibitor was unable to block the cGMP production induced by a NO-donor like 3-morpholinosydnonimine (SIN-1). In conclusion, these results indicate that, depending on the glutamatergic receptors involved, CaM-kinase II could participate in the regulation of NO synthesis in striatal neurones.
Rodriguez-Alvarez
J
J
CNRS-UPR 9023, CCIPE, Montpellier, France.
Lafon-Cazal
M
M
Bockaert
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000187:drug effects*
D004791:Enzyme Inhibitors; D016202:N-Methylaspartate; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019001:Nitric Oxide Synthase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases