title: Nitric oxide increases calcium/calmodulin-dependent phosphorylation of proteins in the postsynaptic density of adult rat cerebral cortex.
abstract: 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.
authors.affiliation: Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, UMDNJ, Piscataway 08854, USA.
authors.forename: K
authors.initials: K
authors.lastname: Wu
authors.forename: J L
authors.initials: JL
authors.lastname: Xu
authors.forename: P C
authors.initials: PC
authors.lastname: Suen
authors.forename: Y Y
authors.initials: YY
authors.lastname: Huang
authors.forename: H T
authors.initials: HT
authors.lastname: Mount
mesh_terms: 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*
chemical_list: 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