THE CHOLINERGIC ‘PITFALL’: ACETYLCHOLINE, A UNIVERSAL CELL MOLECULE IN BIOLOGICAL SYSTEMS, INCLUDING HUMANS

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Abstract
1. Acetylcholine (ACh) represents one of the most exemplary neurotransmitters. In addition to its presence in neuronal tissue, there is increasing experimental evidence that ACh is widely expressed in pro‐ and eukaryotic non‐neuronal cells. Thus, ACh has been detected in bacteria, algae, protozoa, tubellariae and primitive plants, suggesting an extremely early appearance of ACh in the evolutionary process.2. In humans, ACh and/or the synthesizing enzyme, choline acetyltransferase, has been demonstrated in epithelial cells (airways, alimentary tract, urogenital tract, epidermis), mesothelial (pleura, pericardium) and endothelial and muscle cells. In addition, immune cells express the non‐neuronal cholinergic system (i.e. the synthesis of ACh can be detected in human leucocytes (granulocytes, lymphocytes and macrophages)), as well as in rat microgliain vitro.3. The widespread expression of non‐neuronal ACh is accompanied by the ubiquitous expression of cholinesterase activity, which prevents ACh from acting as a classical hormone.4. Non‐neuronal ACh mediates its cellular actions in an auto‐ and paracrine manner via the activation of the widely expressed nicotinic and muscarinic acetylcholine receptors, which can interfere with virtually all cellular signalling pathways (ion channels and key enzymes).5. Non‐neuronal ACh appears to be involved in the regulation of basic cell functions, such as mitosis, cell differentiation, organization of the cytoskeleton, cell–cell contact, secretion and absorption. Non‐neuronal ACh also plays a role in the regulation of immune functions. All these qualities together may mediate the so‐called ‘trophic property’ of ACh.6. Future experiments should be designed to analyse the cellular effects of ACh in greater detail. The involvement of the non‐neuronal cholinergic system in the pathogenesis of chronic inflammatory diseases should be investigated to open up new therapeutic strategies.