Nitric oxide increases calcium/calmodulin-dependent phosphorylation of proteins in the postsynaptic density of adult rat cerebral cortex

• Published in: Brain research. Molecular brain research. 1996-08, Vol.40 (1), p.22-26
• Main Authors: Wu, Kuo, Xu, Jia-ling, Suen, Piin-chau, Huang, Yung-yu, Mount, Howard T.J.
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; Biochemistry and metabolism; Biological and medical sciences; Calcium - metabolism; Calcium - pharmacology; Calcium/calmodulin-dependent phosphorylation; Calmodulin - metabolism; Calmodulin - pharmacology; Central nervous system; Cerebral Cortex - metabolism; Cyclic AMP - metabolism; Fundamental and applied biological sciences. Psychology; l-Arginine; Major postsynaptic density protein; N- l-Arginine-methyl ester; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - metabolism; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - pharmacology; Nitric oxide synthase; Nitric Oxide Synthase - antagonists & inhibitors; Nitroprusside - pharmacology; Nitroso Compounds - pharmacology; Phosphoproteins - metabolism; Phosphorylation; Rats; Rats, Sprague-Dawley; Sodium nitroprusside; Synapse; Synaptic Membranes - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/0169-328X(96)00028-9

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 Ca 2+/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 consitute a feedback mechanism for regulation of NOS activity.