Regulation of neuronal nitric oxide synthase by histone, protamine, and myelin basic protein.
We examined the effects of endogenous basic proteins rich in the amino acid L-arginine on neuronal NO synthase activity by monitoring cyclic GMP formation in intact neuron-like neuroblastoma N1E-115 cells. Histone, protamine and myelin basic protein significantly stimulated cyclic GMP formation, both in a time- and concentration-dependent manner. These effects were blocked by hemoglobin and NO synthase inhibitors. Removal of the extracellular/intracellular Ca2+ gradient by a Ca2+ chelator completely abolished the cyclic GMP responses elicited by histone and protamine, suggesting that influx of extracellular Ca2+ might be involved in their activation of NO synthase. The effects of myelin basic protein on cyclic GMP formation, however, appeared to be due to Ca2+ release from intracellular stores. In cytosolic preparations of rat cerebellum, these basic proteins inhibited the metabolism of L-arginine into L-citrulline by NO synthase. We conclude from our findings that endogenous basic proteins might be involved in the regulation of neuronal NO synthase activity. Their effects on the enzyme could be either stimulatory or inhibitory, depending on whether the basic proteins exert their effects extracellularly or intracellularly, respectively.
Hu
J
J
Division of Neuroscience Research in Psychiatry, University of Minnesota School of Medicine, Minneapolis 55455, USA.
Fridlund
J
J
el-Fakahany
E E
EE
D000594:Amino Acid Oxidoreductases / Q000187:drug effects*; D000818:Animals; D001667:Binding, Competitive; D002118:Calcium / Q000502:physiology; D002956:Citrulline / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D006657:Histones / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D019001:Nitric Oxide Synthase; D011479:Protamines / Q000494:pharmacology; D051381:Rats; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured
D006657:Histones; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D011479:Protamines; D002956:Citrulline; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP; D002118:Calcium