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.