NO functions as an important cellular signaling molecule. It participates to modulate insulin secretion, airway, and vascular tone and has been shown to be involved in angiogenesis and neural development.

Further examples of biological actions of NO in the cardiovascular, nervous, and host defense systems are summarized in Table 1. Only the actions of NO in the cardiovascular system will be discussed in this chapter. After the generation of NO in the endothelial cell by the NOS enzyme, the NO diffuses to an adjacent smooth muscle where it acts as an agonist to initiate biological responses.

Table1. Biological Actions of Nitric Oxide

See Figure 1B. In the endothelial cell, the arrival of the hormone ET-2 activates its membrane receptor which in turn increases the intracellular Ca2+ concentration and as well allows the entrance of Ca2+ into the cell through a Ca2+ permease. The Ca2+ then binds to the Ca2+-binding protein, calmodulin, which interacts with the nitric oxide synthase (NOS) and releases NO. The hormone NO then diffuses through the cell mem brane of the endothelial cell and then diffuses across the cell membrane of a nearby smooth muscle cell and binds to the soluble guanylate cyclase and generates cGMP. At the same time the fatty acid arachidonic acid (AA) stimulates the release of prostacyclin (PGI2), which then diffuses through the endothelial cell plasma membrane followed by an entrance into the smooth muscle cell where it stimulates the adenylate cyclase to produce the second messenger cAMP, which causes the smooth muscle cell to engage in relaxation.

Fig1. The gas, nitric oxide, is a hormone that initiates vasorelaxation and lowers blood pressure. (A) Biochemical properties of the nitric acid synthase enzyme. Nitric acid (NO) is enzymatically produced from the amino acid L-arginine by a Ca2+ dependent NO synthase that is present in many mammalian tissues. The reaction is catalyzed by an NADPH requiring nitric oxide synthase (NOS). The nitrogen donor (colored red) is located on the guanidino group of the side chain of the amino acid substrate L-arginine. The oxygen donor (colored red) is molecular oxygen. The final products of the enzymatic reaction are the release of the gas nitric oxide, NO, and the amino acid L-citrulline. (B) Nitric oxide signalling pathways that generate biological responses in both endothelial cells and smooth muscle cells. Endothelial cells have a variety of supporting signal transduction pathways that lead to the activation of nitrogen oxide synthase, which then diffuses to adjacent smooth muscle cells. Here it enters the cell and, via signal activation, causes the smooth muscle cell to engage in lowering the blood pressure because of reduction of peripheral vascular resistance and at the same time increase. Ultimately the generation of NO leads to relaxation of both the endothelial cells and its partner smooth muscle cell(s). In these cells there is guanylyl cyclase that has a heme group that binds the NO hormone, thus activating the production of the second messenger, cGMP, which results in muscle relaxation.

Virtually all of the known biological actions of NO on the cardiovascular system are mediated by the activation of a soluble guanylate cyclase. The guanylate cyclase has heme as a prosthetic group, and NO binds tightly to this moiety in the smooth muscle cells. The resulting activation of the guanylate cyclase results in the production of cGMP, which is then postulated to have actions on protein kinases, nucleotide-sensitive phosphodiesterases, or ion channels, which are linked to the generation of the smooth muscle response of vasodilation and relaxation.

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مواضيع ذات صلة

Kallikreins and Kinins

Biological Actions of Endothelins

Red Blood Cell Enzymopathies- Metabolic Pathways

Hemoglobins with Decreased Oxygen Affinity

Chemistry, Biosynthesis, and Secretion of Nitric Oxide System

Chemistry, Biosynthesis, and Secretion of Endothelins

Chemistry, Biosynthesis, and Secretion of ANP

Hemoglobins with Increased Oxygen Affinity

Specific Enzymes are Associated with Compartments Separated by the Mitochondrial Membranes

ATP Acts as the “Energy Currency” of The Cell

Living Organisms Package Transition Metals Within Organometallic Complexes

Androgen Biosynthesis