Nitric oxide is a very unusual molecule to be playing a role in physiological regulation. It is a free radical and volatile gas with a half-life in the body measured in seconds.
We have already briefly encountered nitric oxide in the context of oxygen radicals in phagolysosomes. Nitric oxide is synthesized there to interact with the oxygen radicals in killing phagocytized microbes.
But curiously enough, nitric oxide also serves as a neurotransmitter in certain places. However, it is much different than other neurotransmitters in that is can easily diffuse over short distances and affects more than one cell.
Also, in blood vessels nitric oxide is released as a paracrine that relaxes smooth muscle cells. This leads to the dilation of blood vessels.
Nitric oxide synthesis begins when the enzyme nitric oxide synthase(NOS) is activated. This enzyme acts on an amino acid (L-arginine) to create nitric oxide.
There are three forms of nitric oxide synthase, which correspond to its three areas of action, which are in phagocytes, neurons, and endothelial cells of blood vessels.
When the nitric oxide acts as a regulatory molecule, it diffuses to and activates a guanylyl cyclase. Guanylate cyclase converts GTP to cyclic-GMP, which then serves as the second messenger that cause the cellular action. (Note how this is similar to adenylyl cylase and cyclic-AMP)
The diagram to the right shows how activation of the endothelial form of nitric oxide synthase leads to dilation of a blood vessels. The stimulus, for example, might be a regulatory molecule that activates the nitric oxide synthase in the endothelium. The resulting nitric oxide diffuses to the surrounding smooth muscles cells, leading to relaxation of the smooth muscle around the the periphery of the blood vessels. This allows the blood vessel to dilate, leading to greater blood flow.
Several important drug actions revolve around nitric oxide. Nitroglycerin is converted to nitric oxide in the blood, which is why it dilates of blood vessels serving the heart.
Sildenafil (Viagra) and similar drugs specifically block a form of phosphodiestase found in the penis. The function of the phosphodiesterase is remove cyclic-GMP by converting it back to GTP. Thus, sildenafil causes more cyclic-GMP to be present, and thus more dilation of the blood vessels supplying blood to the erectile tissue in the penis .
(Nitric oxide can also be breathed as a gas to dilate blood vessels in the lungs in certain respiratory disorders, although this is primarily an experimental use at present.)
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QUESTION: What is the product formed by activated guanylyl cyclase?
QUESTION: In an endothelium, does activated nitric oxide synthase cause relaxation or contraction of smooth muscle? QUESTION: Does cyclic GMP cause smooth muscle contraction or relaxation? QUESTION: Does sildenafil lead to more or less cyclic GMP? |
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