BIOMAT Database Logo BIOMAT Database Logo

Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. 1992

N E Rogers, and L J Ignarro
Department of Pharmacology, UCLA School of Medicine 90024.

The objective of this study was to determine whether constitutive nitric oxide (NO) synthase from rat cerebellum could be regulated by the two products of the reaction, NO and L-citrulline, utilizing L-arginine as substrate. NO synthase activity was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine in the presence of added cofactors. The rate of citrulline formation in enzyme reaction mixtures was non-linear. Addition of superoxide dismutase (SOD; 100 units) inhibited NO synthase activity and made the rate of product formation more non-linear, whereas addition of oxyhemoglobin (HbO2; 30 microM) increased NO synthase activity, made the rate of product formation linear and also abolished the effect of SOD. Added NO (10 microM) inhibited NO synthase activity and this inhibition was potentiated by SOD and abolished by HbO2. Added L-citrulline (1 mM) did not alter NO synthase activity. The two NO donors, S-nitroso-N-acetylpenicillamine (200 microM) and N-methyl-N'-nitro-N-nitrosoguanidine (200 microM) mimicked the inhibitory effect of NO and inhibition of NO synthase activity by NO was reversible. These observations indicate clearly that NO formed during the NO synthase reaction or added to the enzyme reaction mixture causes a reversible inhibition of NO synthase activity. Thus, NO may function as a negative feedback modulator of its own synthesis.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008751 Methylene Blue A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN. Methylthionine Chloride,Swiss Blue,Basic Blue 9,Chromosmon,Methylene Blue N,Methylthioninium Chloride,Urolene Blue,Blue 9, Basic,Blue N, Methylene,Blue, Methylene,Blue, Swiss,Blue, Urolene
D008769 Methylnitronitrosoguanidine A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties. Methylnitrosonitroguanidine,Nitrosomethylnitroguanidine,Nitrosonitromethylguanidine,MNNG,N-Methyl-N'-nitro-N-nitrosoguanidine,N Methyl N' nitro N nitrosoguanidine
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010108 Oxyhemoglobins A compound formed by the combination of hemoglobin and oxygen. It is a complex in which the oxygen is bound directly to the iron without causing a change from the ferrous to the ferric state. Oxycobalt Hemoglobin,Oxycobalthemoglobin,Oxyhemoglobin,Hemoglobin, Oxycobalt
D010396 Penicillamine 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. Dimethylcysteine,Mercaptovaline,beta,beta-Dimethylcysteine,Copper Penicillaminate,Cuprenil,Cuprimine,D-3-Mercaptovaline,D-Penicillamine,Metalcaptase,D 3 Mercaptovaline,D Penicillamine,Penicillaminate, Copper,beta,beta Dimethylcysteine
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D002956 Citrulline
D006706 Homeostasis The processes whereby the internal environment of an organism tends to remain balanced and stable. Autoregulation

Related Publications

N E Rogers, and L J Ignarro
Biosynthesis of nitric oxide and citrulline from L-arginine by constitutive nitric oxide synthase present in rabbit corpus cavernosum.
July 1992, Biochemical and biophysical research communications,
N E Rogers, and L J Ignarro
Inhibition of purified nitric oxide synthase from rat cerebellum and macrophage by L-arginine analogs.
December 1994, Archives of biochemistry and biophysics,
N E Rogers, and L J Ignarro
Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine.
June 1992, Biochemical and biophysical research communications,
N E Rogers, and L J Ignarro
Chronic inhibition of nitric oxide synthase activity by NG-nitro-L-arginine induces nitric oxide synthase expression in the developing rat cerebellum.
May 2012, Neurochemistry international,
N E Rogers, and L J Ignarro
L-arginine availability is not limiting for nitric oxide generation from recombinant endothelial nitric oxide synthase.
January 1999, Journal of vascular research,
N E Rogers, and L J Ignarro
Inhibition of nitric oxide synthase by L-arginine metabolites.
May 1995, Biochemical Society transactions,
N E Rogers, and L J Ignarro
Inducible nitric oxide synthase expression is inhibited by myeloperoxidase.
August 2005, Nitric oxide : biology and chemistry,
N E Rogers, and L J Ignarro
Selective inhibition of constitutive nitric oxide synthase by L-NG-nitroarginine.
August 1993, Biochemistry,
N E Rogers, and L J Ignarro
Nitric oxide synthase inhibition with NG-mono-methyl-L-arginine reversibly decreases cerebral blood flow in piglets.
March 1994, Critical care medicine,
N E Rogers, and L J Ignarro
Formation of free nitric oxide from l-arginine by nitric oxide synthase: direct enhancement of generation by superoxide dismutase.
November 1994, Proceedings of the National Academy of Sciences of the United States of America,
Copied contents to your clipboard!