ric OxideExpansion on the Recent Discoveries Concerning Nitric Oxideas presented by Dr. Jack R. LancasterNitric Oxide, or NO, its chemical representation, was until recently notconsidered to be of any benefit to the life processes of animals, much lesshuman beings. However, studies have proven that this simple compound had anabundance of uses in the body, ranging from the nervous system to thereproductive system. Its many uses are still being explored, and it is hopedthat it can play an active role in the cures for certain types of cancers andtumors that form in the brain and other parts of the body.
Nitric Oxide is not to be confused with nitrous oxide, the latter ofwhich is commonly known as laughing gas. Nitric oxide has one more electron thanthe anesthetic. NO is not soluble in water. It is a clear gas. When NO isexposed to air, it mixes with oxygen, yielding nitrogen IV dioxide, a brown gaswhich is soluble in water. These are just a few of the chemical properties ofnitric oxide. With the total life expectancy of nitric oxide being from six toten seconds, it is not surprising that it has not been until recently that itwas discovered in the body. The compound is quickly converted into nitrates andnitrites by oxygen and water. Yet even its short-lived life, it has found manyfunctions within the body. Nitric oxide enables white blood cells to kill tumorcells and bacteria, and it allows neurotransmitters to dilate blood vessels. Italso serves as a messenger for neurons, like a neurotransmitter. The compoundis also accountable for penile erections. Further experiments may lead to itsuse in memory research and for the treatment of certain neurodegenerativedisorders. One of the most exciting discoveries of nitric oxide involves itsfunction in the brain. It was first discovered that nitric oxide played a rolein the nervous system in 1982. Small amounts of it prove useful in the openingof calcium ion channels (with glutamate, an excitatory neurotransmitter) sendinga strong excitatory impulse. However, in larger amounts, its effects are quiteharmful. 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 thebrain, scientists used a purification method from a tissue sample of the brain.
One scientist discovered that the synthesis of nitric oxide required thepresence of calcium, which often acts by binding to a ubiquitous cofactor calledcalmodulin. A small amount of calmodulin is added to the enzyme preparations,and immediately there is an enhancement in enzyme activity. Recognition of theassociation between nitric oxide, calcium an calmodulin leads to furtherpurification of the enzyme. When glutamate moves the calcium into cells, thecalcium ions bind to calmodulin and activate nitric oxide synthase, all of theseactivities happening within a few thousandths of a second. After thispurification is made, antibodies can be made against it, and nitric oxide can betraced in the rest of the brain and other parts of the body. The synthasecontaining nitric oxide can be found only in small populations of neurons,mostly in the hypothalamus part of the brain. The hypothalamus is thecontroller of enzyme secretion, and controls the release of the hormonesvasopressin and oxytocin. In the adrenal gland, the nitric oxide synthase ishighly concentrated in a web of neurons that stimulate adrenal cells to releaseadrenaline. It is also found in the intestine, cerebral cortex, and in theendothelial 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. Itstie 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 caudatenucleus degenerate, but no daphorase neurons are lost. In heart strokes and insome brain regions in which there is involvement of Alzheimer’s disease,diaphorase neurons are similarly resistant. Neurotoxic destruction of neuronsin culture can kill ninety percent of neurons, whereas diaphorase neurons remaincompletely unharmed. Scientists studied the perplexity of this issue.
Discerning the overlap between diaphorase neurons and cerebral neuronscontaining 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 makesneurons resist neurotoxec damage. Yet, NO was the result of glutamate activity,which also led to neurotoxicity. The question aroused here is, how could it goboth ways? One supported theory is that in the presence of high levels ofglutamate, nitric oxide-producing neurons behave like macrophages, releasinglethal amounts of nitric oxide. It is then assumed that inhibitors of nitricoxide synthase prevent the neurotoxicity. The neurotoxicity of cerebralcortical neurons were studied to test this theory. NMDA is added to thecultures from the brain cells of rats. One day after being exposed to the NMDAfor only five minutes, up to ninety percent of the neurons were dead. Thisreveals the neurotoxicity that occurs in vascular strokes. It is found throughthese experiments that nitroarginine, which is a very powerful and selectiveinhibitor of nitric oxide synthase, completely prevents the neurotoxicity givenfrom the NMDA. Removing the arginine from the mixture protects the cells. Also,homoglobin, which binds with and inactivates nitric oxide, also acts as aninhibitor to the harmful effects of neurotoxicity. The findings of theseexperiments led to further tests with a direct exposure of lab rats to thenitric oxide synthase. Because NMDA antoagonists can block the damage causedfrom the glutamate associated with heart strokes, it is questioned whethernitric oxide has the ability to modulate the destruction caused by the stroke.
In an experiment performed by Bernard Scatton in Paris, lab rats were injectedwith small doses of nitroarginine immediately after initiating a stroke on therats. The nitroarginine reduced stroke damage by seventy-three percent. Thisfantastic find proves that there is hope in the evolution and search for curesfor vascular strokes. Nitric oxide may also be involved in memory and learning.
Memory involves long-term increases or decreases in transmission across certainsynapses after the repetitive stimulation of neurons. They then can detectpersistent increases or decreases in synaptic transmission. The role of nitricoxide synthase in these processes. The effects of nitric oxide synthaseinhibitors were studied in hippocampus, which is the area of the brain thatcontrols the memory. Due to its many influences, however, further study isneeded to determine exactly what role nitric oxide plays in the memory.
Scientists have high hopes for the further investigations of nitric oxide. Moreexperiments lead to greater knowledge, and the effects of this knowledge arereceiving a warm reception in this day and age of medicine. The knowledgegained by the study of nitric oxide is hoped to lead to cures and betterfighting agents for cancers, tumors, strokes, memory loss, as well as otherbrain diseases, sensory deprivation, intestinal activity, and various otherbiological conditions that are affected by neurotransmission. It is amazingalready the breakthroughs that have surfaced within the past six yearsconcerning the study of nitric oxide, and its further study is excitedly underway.