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Acetylcholine acts as a prominent transmitter in the central and peripheral nervous system. The aim of the present study was to investigate whether mammalian non-neuronal cells can synthesize and store acetylcholine. A cotton tipped applicator (Q-tip) was used to collect surface cells from airways and alimentary tract. Histological inspection indicated that rubbing of the luminal surface of human bronchi did not penetrate the basal membrane. Acetylcholine was measured by an HPLC-method using substrate-specific enzyme reactor-columns. Non-neuronal acetylcholine was found in cells covering inner and outer surfaces of rat and man. For example, acetylcholine was detected in the surface epithelium of human bronchi (33 pmol/g), mouth (female 0.7 and male 8 pmol/sample), small and large intestine (800 and 16 pmol/g, respectively), gall bladder (12 pmol/g), vagina (6 pmol/sample), skin 1000 (pmol/g) and in pulmonary pleura (5 pmol/sample). Somewhat higher amounts of acetylcholine were found in rat tracheal and intestinal epithelium and in rat skin. The synthesizing enzyme choline acetyltransferase (ChAT) was demonstrated in human surface epithelium by immunohistochemistry and by Western blot analysis. Enzymatic ChAT activity was demonstrated in isolated epithelial cells of human bronchi and small intestine (3.5 and 28 nmol/mg protein/h, respectively). Applied acetylcholine (in nM concentrations) increased, whereas inhibition of ChAT activity by bromoacetylcholine (10 microM) reduced the growth of cultured human bronchial epithelial cells. Inhibition of cell growth occurred also in the presence of atropine (1 microM) together with (+/-)-tubocurarine (30 microM). In conclusion, the present experiments demonstrate a widespread existence of non-neuronal acetylcholine in surface cells of man. Non-neuronal acetylcholine may act as a local signalling molecule.

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 microglia in 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.

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