Expansion On The Recent Discoveries Concerning Nitric Oxide

Expansion On The Recent Discoveries Concerning Nitric Oxide

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Expansion on the Recent Discoveries Concerning Nitric Oxide


as presented by Dr. Jack R. Lancaster

     Nitric Oxide, or NO, its chemical representation, was until recently not
considered to be of any benefit to the life processes of animals, much less
human beings. However, studies have proven that this simple compound had an
abundance of uses in the body, ranging from the nervous system to the
reproductive system. Its many uses are still being explored, and it is hoped
that it can play an active role in the cures for certain types of cancers and
tumors that form in the brain and other parts of the body.
     Nitric Oxide is not to be confused with nitrous oxide, the latter of
which is commonly known as laughing gas. Nitric oxide has one more electron than
the anesthetic. NO is not soluble in water. It is a clear gas. When NO is
exposed to air, it mixes with oxygen, yielding nitrogen IV dioxide, a brown gas
which is soluble in water. These are just a few of the chemical properties of
nitric oxide. With the total life expectancy of nitric oxide being from six to
ten seconds, it is not surprising that it has not been until recently that it
was discovered in the body. The compound is quickly converted into nitrates and
nitrites by oxygen and water. Yet even its short-lived life, it has found many
functions within the body. Nitric oxide enables white blood cells to kill tumor
cells and bacteria, and it allows neurotransmitters to dilate blood vessels. It
also serves as a messenger for neurons, like a neurotransmitter. The compound
is also accountable for penile erections. Further experiments may lead to its
use in memory research and for the treatment of certain neurodegenerative
disorders. One of the most exciting discoveries of nitric oxide involves its
function in the brain. It was first discovered that nitric oxide played a role
in the nervous system in 1982. Small amounts of it prove useful in the opening
of calcium ion channels (with glutamate, an excitatory neurotransmitter) sending
a strong excitatory impulse. However, in larger amounts, its effects are quite
harmful. The channels are forced to fire more rapidly, which can kill the cells.
This is the cause of most strokes. To find where nitric oxide is found in the
brain, scientists used a purification method from a tissue sample of the brain.
One scientist discovered that the synthesis of nitric oxide required the
presence of calcium, which often acts by binding to a ubiquitous cofactor called
calmodulin. A small amount of calmodulin is added to the enzyme preparations,

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and immediately there is an enhancement in enzyme activity. Recognition of the
association between nitric oxide, calcium an calmodulin leads to further
purification of the enzyme. When glutamate moves the calcium into cells, the
calcium ions bind to calmodulin and activate nitric oxide synthase, all of these
activities happening within a few thousandths of a second. After this
purification is made, antibodies can be made against it, and nitric oxide can be
traced in the rest of the brain and other parts of the body. The synthase
containing nitric oxide can be found only in small populations of neurons,
mostly in the hypothalamus part of the brain. The hypothalamus is the
controller of enzyme secretion, and controls the release of the hormones
vasopressin and oxytocin. In the adrenal gland, the nitric oxide synthase is
highly concentrated in a web of neurons that stimulate adrenal cells to release
adrenaline. It is also found in the intestine, cerebral cortex, and in the
endothelial layer of blood vessels, yet to a smaller degree.
     Although the location of nitric oxide was found by this experimentation,
it wasn’t until later that the function of the nitric oxide was studied. Its
tie to other closely related neurons did shed some light on this. In Huntington’
s disease up to ninety-five percent of neurons in an area called the caudate
nucleus degenerate, but no daphorase neurons are lost. In heart strokes and in
some brain regions in which there is involvement of Alzheimer’s disease,
diaphorase neurons are similarly resistant. Neurotoxic destruction of neurons
in culture can kill ninety percent of neurons, whereas diaphorase neurons remain
completely unharmed. Scientists studied the perplexity of this issue.
Discerning the overlap between diaphorase neurons and cerebral neurons
containing nitric oxide synthase was a good start to their goal. First of all,
it was clear that there was something about nitric oxide synthesis that makes
neurons resist neurotoxec damage. Yet, NO was the result of glutamate activity,
which also led to neurotoxicity. The question aroused here is, how could it go
both ways? One supported theory is that in the presence of high levels of
glutamate, nitric oxide-producing neurons behave like macrophages, releasing
lethal amounts of nitric oxide. It is then assumed that inhibitors of nitric
oxide synthase prevent the neurotoxicity. The neurotoxicity of cerebral
cortical neurons were studied to test this theory. NMDA is added to the
cultures from the brain cells of rats. One day after being exposed to the NMDA
for only five minutes, up to ninety percent of the neurons were dead. This
reveals the neurotoxicity that occurs in vascular strokes. It is found through
these experiments that nitroarginine, which is a very powerful and selective
inhibitor of nitric oxide synthase, completely prevents the neurotoxicity given
from the NMDA. Removing the arginine from the mixture protects the cells. Also,
homoglobin, which binds with and inactivates nitric oxide, also acts as an
inhibitor to the harmful effects of neurotoxicity. The findings of these
experiments led to further tests with a direct exposure of lab rats to the
nitric oxide synthase. Because NMDA antoagonists can block the damage caused
from the glutamate associated with heart strokes, it is questioned whether
nitric oxide has the ability to modulate the destruction caused by the stroke.
In an experiment performed by Bernard Scatton in Paris, lab rats were injected
with small doses of nitroarginine immediately after initiating a stroke on the
rats. The nitroarginine reduced stroke damage by seventy-three percent. This
fantastic find proves that there is hope in the evolution and search for cures
for vascular strokes. Nitric oxide may also be involved in memory and learning.
Memory involves long-term increases or decreases in transmission across certain
synapses after the repetitive stimulation of neurons. They then can detect
persistent increases or decreases in synaptic transmission. The role of nitric
oxide synthase in these processes. The effects of nitric oxide synthase
inhibitors were studied in hippocampus, which is the area of the brain that
controls the memory. Due to its many influences, however, further study is
needed to determine exactly what role nitric oxide plays in the memory.
Scientists have high hopes for the further investigations of nitric oxide. More
experiments lead to greater knowledge, and the effects of this knowledge are
receiving a warm reception in this day and age of medicine. The knowledge
gained by the study of nitric oxide is hoped to lead to cures and better
fighting agents for cancers, tumors, strokes, memory loss, as well as other
brain diseases, sensory deprivation, intestinal activity, and various other
biological conditions that are affected by neurotransmission. It is amazing
already the breakthroughs that have surfaced within the past six years
concerning the study of nitric oxide, and its further study is excitedly under
way.
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