Biological properties and mechanisms of nicotine

Biological properties and mechanisms of nicotine

 

■   Biological properties 

Nicotine, found in cigarettes, is the main substance responsible for addiction, causing cravings and withdrawal symptoms in both humans and animals. It shares many similarities in molecular structure, brain anatomy, and pharmacological effects with other addictive drugs, particularly those that improve cognitive function. Nicotine primarily acts by binding to specific nicotinic acetylcholine receptors in the brain, which leads to increased release and metabolism of acetylcholine (Ach). Additionally, nicotine stimulates the dopaminergic system, leading to elevated levels of dopamine. These physiological effects and mechanisms contribute to reinforcing behavioral changes and fostering dependence on nicotine (1). 

< Nicotine, the main substance responsible for smoking addiction>

 

■   Biological mechanisms

Nicotine is known to mediate its effects on the nervous system through neurotransmitters such as GABA, serotonin, noradrenaline, and brainstem cholinergic systems.

Primarily, nicotine acts on the cardiovascular system by stimulating the sympathetic nervous system, leading to the release of noradrenaline. This results in increased heart rate, blood pressure, myocardial contractility, and overall systemic vascular constriction. Additionally, stimulation of nicotinic acetylcholine receptors (nAChRs) expressed in the autonomic nervous system ganglia can also influence cardiovascular regulation (2, 3).

Exposure to nicotine through smoking acts as an environmental trigger, contributing to the development of several autoimmune diseases. This is primarily due to nicotine's ability to increase the production of free radicals, which can lead to DNA modifications and subsequent autoimmunity. Additionally, nicotine can cause protein citrullination, leading to the production of autoantibodies (4, 5).

Nicotine present in cigarettes can also form carcinogens by reacting with air pollutants or through metabolic processes, forming covalent bonds. These carcinogens can induce DNA coding errors and permanent mutations in the human body, making nicotine a central player in chemical carcinogenesis. When these mutations occur in critical regions of genes responsible for regulating cell growth, such as oncogenes and tumor suppressor genes, it disrupts normal cell proliferation mechanisms, leading to genomic instability and cancer development. A study analyzing 623 cancer-related genes in 188 human lung adenocarcinomas supported this theory, revealing multiple somatic mutations consistent with chronic exposure to cigarette smoke carcinogens and metabolically active forms (6, 7).

Nicotine itself is not classified as a carcinogen. However, continued cigarette use leads to addiction and exposes the body to carcinogens and toxic substances. According to the International Agency for Research on Cancer (IARC), cigarette smoke contains over 60 carcinogens based on animal experiments. Among these, 16 are classified as carcinogenic to humans (Group 1) (7, 8).

 

■    References

1. Benowitz NL. Neurobiology of nicotine addiction: implications for smoking cessation treatment. Am J Med. 2008 Apr;121(4 Suppl 1):S3-10.

2. Price, L. R., & Martinez, J. (2019). Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature. F1000Research, 8, 1586. https://doi.org/10.12688/f1000research.20062.2

3. Li YF, LaCroix C, Freeling J: Specific subtypes of nicotinic cholinergic receptors involved in sympathetic and parasympathetic cardiovascular responses. Neurosci Lett. 2009; 462(1): 20–23.

4. Gomes, J. P., Watad, A., & Shoenfeld, Y. (2018). Nicotine and autoimmunity: The lotus' flower in tobacco. Pharmacological research, 128, 101–109.

5.  Carlo Perricone, Mathilde Versini, Dana Ben-Ami, Smadar Gertel, Abdulla Watad, Michael J. Segel, Fulvia Ceccarelli, Fabrizio Conti, Luca Cantarini, Dimitrios P. Bogdanos, Alessandro Antonelli, Howard Amital, Guido Valesini, Yehuda Shoenfeld. Smoke and autoimmunity: The fire behind the disease, Autoimmunity Reviews, 2016; 15 (4):, 354-374,

6. Ding L, Getz G, Wheeler DA et al. (2008). Somatic mutations affect key pathways in lung adenocarcinoma. Nature, 455: 1069–1075. doi:10.1038/nature07423 PMID:18948947

7. IARC. IARC Monographs 100E TOBACCO SMOKING.(2018) Available at https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono100E-6.pdf [accessed 23 August 2022]

8.  Schuller HM (2009). Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer, 9: 195–205.