ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract: To clarify the regulatory mechanism of the N-methyl-d-aspartate (NMDA) receptor/channel by several protein kinases, we examined the effects of purified type II of protein kinase C (PKC-II), endogenous Ca2+/calmodulin-dependent protein kinase II (CaMK-II), and purified cyclic AMP-dependent protein kinase on NMDA receptor/ channel activity in the postsynaptic density (PSD) of rat brain. Purified PKC-II and endogenous CaMK-II catalyzed the phosphorylation of 80–200-kDa proteins in the PSD and l-glutamate-(or NMDA)-induced increase of (+)-5-[3H]methyl-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5, 10-imine maleate ([3H]MK-801; open channel blocker for NMDA receptor/channel) binding activity was significantly enhanced. However, the pretreatment of PKC-II-and CaMK-II-catalyzed phosphorylation did not change the binding activity of l-[3H]glutamate, cis-4-[3H](phospho-nomethyl)piperidine-2-carboxylate ([3H]CGS-19755; competitive NMDA receptor antagonist), [3H]glycine, α-[3H]-amino-3-hydroxy-5-methyl-isoxazole-4-propionate, or [3H]-kainate in the PSD. Pretreatment with PKC-II-and CaMK-II-catalyzed phosphorylation enhanced l-glutamate-induced increase of [3H]MK-801 binding additionally, although purified cyclic AMP-dependent protein kinase did not change l-glutamate-induced [3H]MK-801 binding. From these results, it is suggested that PKC-II and/or CaMK-II appears to induce the phosphorylation of the channel domain of the NMDA receptor/channel in the PSD and then cause an enhancement of Ca2+ influx through the channel.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1471-4159.1993.tb03542.x
