It is known that Nitric Oxide (NO) is not only generated by blood vessels cells but also by nerve cells. NO acts as a vital communicator and signal molecule in the human brain and other body parts. It basically acts as a neurotransmitter – a chemical signal which is passed on from one neuron to another. Neurons are indeed the most communicative cells in the body that are involved in the constant flow of information that takes place amongst them. The language of communication is of course chemical.
These chemical signals alter the interaction among the brain’s neurons which ultimately control scellular chemistry and orchestrates the working of various organs. Neurotransmitters are known to be of three types. The first type constitutes amines like acetylcholine, norepinephrine and serotonin. There are organic molecules whose nitrogen group mainly takes part in the signaling process. The second group includes some amino acids—the building blocks of proteins like glycine and glutamic acid or glutamate. Peptides like endorphins are third type of neurotransmitters, which are essentially small protein molecules. All these classic neurotransmitters are actually stored in small vesicles present within the nerve endings. Once released at the synapse, the neurotransmitters bind to specific receptor molecules present on the dendrites of the adjacent neurons.
The chemical message is thus passed on to another neuron and this neuronal signal transmission, is ultimately manifested in some action or thought process of our body. For example, low levels of serotonin in parts of the brain predisposes such individuals to act on suicidal thoughts. Similarly, norepinephrine flows through the brain stimulating adrenalin that is responsible for alertness in the body and helps in mental focus and muscle performance, while its low levels cause anxiety, lack of focus, and sleepiness. Phenylethylamine, which is also found in chocolate, gives us a feeling of bliss. Abnormal levels of neurotransmitters, either excessively high or abnormally low levels are infamous for the origin of several disorders.
Unlike other neurotransmitters, NO, which is a gas, cannot be stored in synaptic vesicles. In fact, it is so unstable that it gets converted to nitrate and nitrite within seconds. For the synthesis of No and enzyme called NO synthase is present in the neurons which forms NO from the amino acid, Arginine. Once released, NO passes out of the neuron’s cell surface and comes in contact with adjacent neurons and simply diffuses into them. But exactly how NO takes part in the brain’s activities is breathtaking.
Glutamate is the major neurotransmitter released in brain neurons. It acts by stimulating the formation of molecules called second messengers like cAMP. It is now clear that it is the presence of the signaling molecule, NO, that enables glutamate to stimulate cAMP formation which further brings changes in the cellular machinery. Today, scientists have even deciphered, at molecular level, how glutamate stimulates NO formation in split seconds to convey signals from one neuron to another. When glutamate is released at synapse, it binds to its receptor molecule present on the dendrite of adjacent neuron. This binding opens up channels which allow the entry of calcium ions into the cell. Once inside the cell, calcium binds to a protein, calmodium, which is a crucial part of NO synthase and controls its enzymatic functioning. As NO synthase is turned on, NO is released.
Excessive release of glutamate may, however, damage neutrons especially in cases of a stroke caused by blood clots in arteries of the brain. Drugs which block the glutamate receptor, or alternatively, inhibitors of NO-synthase markedly help in preventing nerve damage due to stroke. Nitroarginine, a potent inhibitor of NO synthase comes to the rescue of such patients. This is indeed a novel way of treating human stroke victims. NO is a vital neurotransmitter, in not just the brain’s neurons but all nerve cells of the involuntary nervous system throughout the body. NO releasing neurons have been found throughout the gastro-intestinal tract. The network of such neurons which regulates the entire process of digestion is called the myenteric plexus. These nerves regulate the contraction and relaxation of the muscular wall of intestines.
The role of NO as signaling molecule in the normal functioning of male penis is yet another striking finding. As NO regulates dilation of blood vessels in penis, the erection of penis occurs only when specific NO-releasing neurons become active. Based on this knowledge, new drugs against impotence are being developed. NO is also found to be released by macrophages—a type of white blood cells which are active in inflammation. These cells are a source of No when the body is attacked by harmful substances. Macrophages then engulf and kill the invading foreign particles as well as tum or cells. Drugs which stimulate the function of NO synthase can, therefore, regulate the activity of macrophages.
As NO-releasing neurons are present throughout the body and regulate diverse biological activities, the therapeutic potential of drugs that stimulate or inhibit the formation of NO knows no boundaries. Harnessing the immense potential of this finding pharmaceutical companies all over the world are working on developing drugs which can suitably manipulate the release of NO and rescue the human body from diverse forms of illnesses. Understandably, all this has stemmed from the Nobel prize winning discovery that NO, a notorious air pollutant, is actually a good Samaritan molecule which causes vital signaling in biological systems. An ironical fact, indeed!