Inducible NO synthase enzyme

Inducible NO synthase (iNOS) is usually not constitutively expressed, but can be induced in macrophages by bacterial lipopolysaccharide (LPS), cytokines and other-agents. Although primarily identified in macrophages, expression of the enzyme can be stimulated in virtually any cell or tissue, provided the appropriate inducing agents have been identified (for review see [1] and [3]). 

Before discussing some of the observations concerning -NO in our laboratory, it is important to review a few of the basic principles of "NO production and mechanism of action. More detail on these topics can be found in other chapters in this book. First, "NO production can occur by one of two categories of NOS enzymes. Constitutive enzymes are expressed in various cell types, including endothelial cells, neurons, and neutrophils. Production of "NO by this type of enzyme is typically calcium/calmodulin-dependent and occurs immediately. This type of production has also been referred to as low output. Cells such as macrophages, hepatocytes, and smooth muscle cells express an inducible NO synthase. The induction of this enzyme typically results from exposure of the cells... 

ACE inhibitors inhibit the degradation of bradykinin and potentiate the effects of bradykinin by about 50-100-fold. The prevention of bradykinin degradation by ACE inhibitors is particularly protective for the heart. Increased bradykinin levels prevent postischemic reperfusion arrhythmia, delays manifestations of cardiac ischemia, prevents platelet aggregation, and probably also reduces the degree of arteriosclerosis and the development of cardiac hypertrophy. The role of bradykinin and bradykinin-induced NO release for the improvement of cardiac functions by converting enzyme inhibitors has been demonstrated convincingly with use of a specific bradykinin receptor antagonist and inhibitors of NO-synthase. 

Three isoforms of NO synthesizing enzymes ( nitric oxide synthase (NOS)) were isolated, purified, and cloned neuronal NO synthase ( neuronal nitric oxide synthase (nNOS) or isoform (I), immunological or inducible NOS ( inducible (immunological) nitric oxide synthase (iNOS) or isoform (II), and endothelial NOS ( endothelial nitric oxide synthase (eNOS) or isoform... 

NO synthases (NOS, L-arginine, NADPH oxygen oxi-doreductases, nitric oxide forming EC 1.14.13.39) represent a family of enzymes that catalyze the formation of nitric oxide (NO) from the amino acid L-arginine. In mammals, three isoforms of NOS have been identified. They are termed neuronal NOS (nNOS, NOS I, NOS1), inducible NOS (iNOS, NOS H, NOS2), and endothelial... 

In contrast to well-described neuronal, endothelial, and inducible isoforms of NO synthase, mitochondrial NO synthase (mtNOS) is still not fully identified enzyme. As early as 1995, it has been reported that this NOS isoform is located to the inner mitochondrial membrane in... 

As shown in Figure 5.5, nitric oxide is synthesized from the amino acid arginine under the influence of nitric oxide synthase (NOS). This enzyme exists in several tissues as either a constitutive or inducible protein (iNOS). 

There are cytosolic and membrane-bound isoforms of NO synthase. Certain soluble and particulate isoforms are constitutive and other soluble isoforms are inducible. The constitutive enzyme is, by definition, present in the catalytically active form and needs only to be stimulated by an appropriate chemical species, following which there is immediate formation of NO plus L-citrulline. This form of NO synthase requires calcium, and for the most part calmodulin, for stimulation of enzymatic activity. It is likely that an increase in intracellular free calcium in the presence of calmodulin is the signal for stimulation of NO synthase, and therefore, the production of NO. This view is consistent with the general understanding that, in vascular tissue, all endothelium-dependent vaso-... 

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