Nitric oxide increases calcium/calmodulin-dependent phosphorylation of proteins in the postsynaptic density of adult rat cerebral cortex.
Nitric oxide (NO) plays important roles in diverse processes, including neurotransmission in the peripheral and central nervous systems. Nitric oxide synthase (NOS), the enzyme that catalyzes formation of NO from L-arginine, is an intrinsic component of the postsynaptic density (PSD), a specialization of the postsynaptic membrane. This raises the possibility that NO may play a role in postsynaptic function. To begin defining postsynaptic actions of NO, we examined effects of NO on Ca2+/calmodulin-dependent phosphorylation (C/C-DP) of proteins in the cortical PSD of adult rat brain. Treatment of the PSD with sodium nitroprusside, a NO donor, caused a 4-fold increase in C/C-DP of the major PSD protein (mPSDp), relative to C/C treatment alone. Another NO donor, S,S'-dinitrosodithiol, elicited a 2-fold increase in C/C-DP of the mPSDp. Treatment of PSD fractions with L-arginine, a substrate for endogenous NOS, caused a 3-fold increase in C/C-DP activity. The competitive NOS inhibitor, N-L-arginine-methyl ester, decreased basal C/C-DP of cortical mPSDp by 50% and blocked the increase elicited by L-arginine. The inhibitor had no effect on cAMP-dependent phosphorylation, suggesting specificity of NO action on C/C-DP. Our observations indicate that NO enhances C/C-DP of PSD proteins. As C/C-DP inactivates NOS, our findings raise the possibility that NO effects on C/C-DP constitute a feedback mechanism for regulation of NOS activity.
Wu
K
K
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway 08854, USA.
Xu
J L
JL
Suen
P C
PC
Huang
Y Y
YY
Mount
H T
HT
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000378:metabolism*
D002147:Calmodulin; D009419:Nerve Tissue Proteins; D009603:Nitroso Compounds; D010750:Phosphoproteins; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester