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,
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