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Stimulatory Effects of Protein Kinase C and Calmodulin Kinase II on N ‐Methyl‐ d ‐Aspartate Receptor/Channels in the Postsynaptic Density of Rat Brain
Author(s) -
Kitamura Yoshihisa,
Miyazaki Atsuhiro,
Yamanaka Yojiro,
Nomura Yasuyuki
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03542.x
Subject(s) - nmda receptor , protein kinase a , protein kinase c , postsynaptic density , glutamate receptor , ampa receptor , phosphorylation , calmodulin , biology , biochemistry , chemistry , microbiology and biotechnology , receptor , enzyme
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 Ca 2+ /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‐[ 3 H]methyl‐10, 11‐dihydro‐5 H ‐dibenzo[a, d]cyclohepten‐5, 10‐imine maleate ([ 3 H]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 ‐[ 3 H]glutamate, cis ‐4‐[ 3 H](phospho‐nomethyl)piperidine‐2‐carboxylate ([ 3 H]CGS‐19755; competitive NMDA receptor antagonist), [ 3 H]glycine, α‐[ 3 H]‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate, or [ 3 H]‐kainate in the PSD. Pretreatment with PKC‐II‐and CaMK‐II‐catalyzed phosphorylation enhanced l ‐glutamate‐induced increase of [ 3 H]MK‐801 binding additionally, although purified cyclic AMP‐dependent protein kinase did not change l ‐glutamate‐induced [ 3 H]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 Ca 2+ influx through the channel.