Expansion On The Recent Discoveries Concerning Nitric Oxide Essay, Research Paper

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 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.