Effects of Nicotine On Cell Cillia

Introduction to Nicotine

Nicotine(C10H14N2) is a naturally occurring true alkaloid molecule found in tobacco plants. An alkaloid is a class of organic nitrogenous compounds in plants which have prominent physiological impacts on humans. These include, but are not limited to, the inhibition and activation of enzymes, a pronounced effect on nucleic acid and protein synthesis, and effects on membrane structure and cytoskeletal structure and nerve transmission and induction. Nicotine has gained notoriety in public life due to its addictive nature, which is a direct result of its agonistic behavior in the human brain and nervous system. Nicotine acts as a receptor agonist, a chemical that binds to a receptor and elicits a biological response. Nicotine acts as an agonist to Nicotinic acetylcholine receptors, or nAChRs, a class of receptor polypeptides that respond to the neurotransmitter acetylcholine in the human body. Nicotine competitively binds to these receptors, as it mimics the effects of acetylcholine. These receptors are found in both nervous systems in the human body, as well as muscles and tissues of the human body. They are the primary receptors at the neuromuscular junction in muscles, and are the primary site of nerve and muscle communication. These receptors get their name from nicotine, as nicotine selectively binds to these nicotinic receptors rather than the other receptors in the area. Nicotine is a stimulant, a class of substances that increase physiological and nervous activity in the body. Nicotine stimulates the central nervous system and in turn causes the body to release several neurotransmitters, such as dopamine, acetylcholine, serotonin, and norepinephrine. However, nicotine only causes a brief uptick in neurotransmitter activity and presence; and the constant activation of these receptors and spike in neurotransmitter activity creates the need for more nicotine to be ingested in order to achieve the same effect due to a newly developed drug tolerance. As nicotine stimulates the secretion of these neurotransmitters and receptor activity, the human body is trained to associate a pleasurable response with the usage of nicotine. This activation of the brain's reward pathways; coupled with the stimulation of the adrenal glands, helps create its addictive nature as we become more and more inclined to garner that positive physiological response.

Nicotine is most commonly absorbed through the lungs in the form of smoke, or through smokeless forms of absorption in mucous membranes in the mouth such as chewing tobacco. When used for smoking cessation purposes, or nicotine replacement therapy (NRT), it may be absorbed through buffered alkaline pH systems such as nicotine gum that allow for slower nicotine absorption through cell membranes due to a more gradual integration of nicotine into the bloodstream. Another NRT method, nicotine patches, can be absorbed through the skin in nicotine patches. However, the rate of release into the bloodstream is contingent on many factors, such as permeability of the skin, rate of diffusion, and the rate of nicotine absorption in differing transdermal systems. In consumption outside of NRT, nicotine is metabolized and absorbed very quickly in the body. For example, nicotine absorbed while smoking often reaches the brain in 10 to 20 seconds after the initial puff of a cigarette. This rapid absorption in turn creates behavioral reinforcement that is quick and easy to create, and this rapidity allows the user to modify the amount of nicotine absorbed, as well as the corresponding effects with the raised level of absorption. This method of modification makes smoking the most dependent form of nicotine addiction, as building tolerance coupled with the modification of intake rapidly accelerates the amount of nicotine needed to garner positive reinforcement. Nicotine absorption is largely dependent on pH. Nicotine has a pKa value of 8.0, making it a weak base. When nicotine is ionized, nicotine crosses membranes much slower than when in its unionized form. Therefore, depending on the method of nicotine consumption, the rate of absorption can be significantly faster or slower. For example, nicotine found in many standard American cigarettes is coupled with an acidic, flue-cured cigarette smoke (pH 5.5-6.0), which generates an ionized form of nicotine that will be slowly and minimally absorbed through the mouth, even if held there for a prolonged period of time. In comparison, nicotine coupled with air-cured tobacco smoke, the tobacco found in cigars and some European cigarettes is more basic (6.5 pH or higher), generating a considerable presence of unionized nicotine. Because nicotine in this type of smoke is generally in its unionized state, it is more readily absorbed through the mouth, negating the necessity for nicotine exposure to the respiratory system for proper absorption. Due to the minimal absorption through the mouth when smoking standard American cigarettes, the integration of nicotine into the respiratory system is necessary for absorption. The aerial pathways found in the lungs and alveoli provide a large surface area and tight airways allowing for nicotine concentration to be evenly distributed throughout the respiratory tract. Alongside this even distribution, the basic fluid (7.4 pH) in the human lung allows for nicotine to become about 69% ionized and 31% unionized. This larger presence of unionized nicotine molecules promotes a faster transfer of nicotine across cellular membranes, and the distribution of molecules into the bloodstream, which also provides a basic pH of 7.4. This distribution in turn allows nicotine molecules to bind to receptors in sites such as the liver, kidney, spleen, and lung, leading to potentially damaging effects at these sites. As noted above, after absorption into the bloodstream, nicotine binds to nicotinic receptors at these organ sites and at other neuromuscular junctions. The activation of these sites sends signals to the brain that promote neurotransmitter emission and the stimulation of the sympathetic nervous system, leading to pleasurable effects coupled with stimulating effects such as higher heart rate and increases alertness.

Nicotine has been a cause of discussion due to its potentially harmful effects on human cells and microbial cells, as well as its adverse physiological effects. Nicotine has been found to potentially help the development of cancerous cells, as it allows for increased cancer cell survival and proliferation due to its stimulation of nAChRs. Through the activation of particular signal transduction pathways, nicotine allows for damaged cells to survive. Nicotine forms arachidonic acid metabolites which can cause a large increase in cell division, which is extremely problematic when the body is faced with rapid cancer cell growth and division. Chewing tobacco can lead to inflammation of the human gums, which leads to increased risk of endogenous nitrosation, a process capable of generating carcinogenic N-nitroso compounds in humans. The nitrosation of nicotine can lead to the formation of various carcinogens such as N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). This is especially prevalent in chewing tobacco users as the inflammation of the gums, combined with the increased risk of carcinogen formation due to the presence of nicotine could lead to an increased risk of cancer. As nicotine is very addictive, a lack of the drug may also lead to withdrawal symptoms such as headaches, anxiety, depression, and severe nausea, to name a few. Nicotine also puts users at increased risk of heart attacks as it has been suggested that it may lead to the hardening of arterial walls. There are also many immediate negative effects of nicotine, such as nausea, diarrhea, vomiting, and abdominal pain. Nicotine increased blood pressure and heart rate, which may also lead to increased risk for cardiovascular dysfunction. However, the effects of nicotine may not all be bad. Nicotine has been shown to increase cognitive function and increase alertness, increase relaxation, and is being researched as a possible remedy for several disorders such as Alzheimer’s Disease, Attention Deficit Hyperactivity Disorder, and Parkinson’s Disease. Nicotine’s activation of the brain’s reward and pleasure center is a main culprit as to why nicotine is so addictive, and a main reason why many patients with various mental health disorders have used it to self-medicate. This contradiction of short term positive effects and potential long term negative effects are a large reason why nicotine has become such an interesting chemical for scientists to research.

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Legend/credit: A singular molecule of Nicotine. Nicotine is a naturally occurring true alkaloid found in tobacco. It is consisted of ten carbon atoms, fourteen hydrogen atoms, and two nitrogen atoms.
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Edited by [Author Name], student of Joan Slonczewski for BIOL 116 Information in Living Systems, 2020, Kenyon College.