Mechanisms of Disease: Nicotine -- A Review of its Actions in the Context of Gastrointestinal Disease

Gareth AO Thomas; John Rhodes; John R Ingram


Nat Clin Pract Gastroenterol Hepatol. 2005;2(11):536-544. 

In This Article

The Metabolism and Pharmacologic Actions of Nicotine

Nicotine is the principal alkaloid in tobacco. It is rapidly absorbed through the lungs, skin and gut, and metabolized mainly by the liver to cotinine and other metabolites, some of which are also pharmacologically active. Nicotine is highly addictive, which explains a smoker's craving for tobacco. An average cigarette contains 9-15 mg of nicotine, but only 1 mg or so is absorbed. Shortly after smoking, venous levels of nicotine range from 5 to 30 ng/ml, whereas arterial peaks can be as high as 80 ng/ml. The half-life of nicotine is only about 2 h, whereas that of cotinine is about 18 h.

Nicotine exerts its effects by activating nicotinic acetylcholine receptors (nAChRs), which are classically found in the autonomic ganglia, central nervous system, neuromuscular junction, and adrenal medulla. These receptors have also been identified in non-neuronal tissue, such as keratinocytes in skin,[3] in the bronchial epithelium,[4] and on cells involved in inflammation, such as monocytes, dendritic cells, and microglial cells.[5,6,7] They have also been described in the mucosal epithelium, enteric ganglia, nerves and lymphoid tissue of human small and large bowel.[8,9] The principal role of nAChRs is to transmit signals for the neurotransmitter acetylcholine, and various receptor subtypes appear to perform important physiologic roles that are probably pertinent to the mechanisms involved in some disease processes.

The in vivo actions of nicotine are complex and depend on many factors, including the mode of administration, dose, target organ (i.e. receptor subtype), prevalent autonomic tone and prior sensitization. Nicotine acts through three main mechanisms. First, it produces a biphasic effect on ganglionic transmission, with initial transient stimulation followed by a more persistent depression of all autonomic ganglia. Second, by acting on nAChRs on chromaffin cells, and neuronal cell bodies and terminals, it releases catecholamines from the adrenal medulla and postganglionic sympathetic neurons. Third, it stimulates nAChRs in the central nervous system. The role of nAChRs on non-neurologic tissue such as keratinocytes and monocytes is less clear, but in the former they might facilitate cell-to-cell communication,[3,10] and in the latter they have an immunomodulatory effect.[5]

There have been conflicting results on the effects of nicotine on various biological systems, including the gastrointestinal tract, which might be explained by the complexities of its absorption, its numerous actions, and different experimental study designs. The role of nicotine in human disease remains speculative; conclusions based on observations from in vitro or animal studies might not be directly applicable to human disease.


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