Nitric oxide produced by the oxidation of arginine exists in three isomer forms. The nitric oxide found in the endothelial cells is NOS-3. One that is involved in neuronal pathways is named as NOS-1, and the third one is an inducible form named as NOS-2. NOS-, and NOS-3 are secreted in the presence of calcium and produce gas at low levels for the cell signaling pathway. NOS-2 does not depend on calcium and releases a huge amount of gas that can act as cytotoxic. These chemical compounds serve the purpose of messengers in the transmission of signals through neurons, vasodilation, anti-tumor pathways, and anti-pathogenic pathways. An optimal level of nitric oxide in the body is essential to avoid ischemic damage to the liver. However, when there is an excess of nitric oxide production, it can lead to tissue toxicity resulting in damage to the tissues and septic shock. Excessive secretion of NO is also the cause of many diseases and disorders like juvenile diabetes, multiple sclerosis, ulcerative colitis, and arthritis.
Nitric Oxide and Signaling:
Nitric oxide signaling happens in autocrine and paracrine mechanisms to distribute the biological function of NO throughout the body. This signaling pathway regulates various biological functions with NO acting as a messenger. Though nitric oxide has a different role to play, its role in the cardiovascular system is widely studied. It has both lipophilic and hydrophilic properties to exert its effect on different parts of the body. The signaling pathways always start with a neurotransmitter. The most common neurotransmitter is acetylcholine. When acetylcholine is released, the endothelial cells are activated which in turn activates the GPCR receptor that binds the acetylcholinemolecule. There is a series of downstream proteins and receptors that get activated. GPCR activation trigger the phospholipase C molecule that catalyzes to synthesis IP3. This IP3 moves into the cytoplasm of the cell and causes the voltage-gated calcium channels situated in the endoplasmic reticulum to open and liberate the calcium ions in the endoplasmic reticulum. This free calcium attaches to the calmodulin molecule to generate a complex of calcium-calmodulin. This activates the enzyme nitricoxide synthase present in the endothelial cells. This catalyzes the production of nitricoxide. This gas diffuses into the smooth muscle surrounding the endothelial cells and it attaches to the guanylate cyclase. Guanylate cyclase in its active form results in the conversion of GTP to GMP. GMP molecules further activate PKG which are myosin components causing the relaxation of smooth muscles of the heart. This PKG also acts by inhibiting the calcium influx as a feedback mechanism. In addition to the role of NO in the cardiovascular system, it is involved in the mediation of various cell signaling pathways of the nervous system. It is known to improve long-term memory for learning by acting as a reverse transmitter in the nervous system. Though there are detailed pathways involving the NO, some of its role in the immune system and sensory system pathways are unknown. There are numerous researches happening with NO as the major messenger in signal transduction.
Effects of abnormal levels of Nitric Oxide:
When there is an abnormal level of nitric oxide or its bio availability is less, a range of symptoms develop. They are hypertension, vascular resistance, thrombosis, stenosis, coronary vasospasm, and many more. All these symptoms gradually lead to diseases such as heart failure, diabetes, hypertension, and atherosclerosis. When high levels of NO are maintained in the body, it leads to toxic effects on the tissue resulting in septic shock. By understanding the role of NO in various diseases, suitable drugs have been developed.
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