Acetylcholine beyond neurons: The non-neuronal cholinergic system in humans

British Journal of Pharmacology

Volumn 154, Issue 8, 2008, Pages 1558-1571

  Wessler, I ^a,b   Kirkpatrick, C J ^a  

^a JOHANNES GUTENBERG UNIVERSITY   (Germany)

^b UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

ACh; ChAT; Epithelial, endothelial, mesenchymal cells; Immune cells; Inflammation; Nicotinic and muscarinic receptors; Non neuronal cholinergic system; Phenotype cell functions; Signal transduction

Indexed keywords

ACETYLCHOLINE; ACETYLCHOLINESTERASE; ATROPINE; CHOLINE; CHOLINERGIC RECEPTOR; MUSCARINIC RECEPTOR; NICOTINIC RECEPTOR; TUBOCURARINE CHLORIDE;

ACETYLCHOLINE RELEASE; ALGA; BACTERIUM; CELL COMMUNICATION; CELL DEATH; CELL DIFFERENTIATION; CELL MIGRATION; CELL PROLIFERATION; CHOLINERGIC ACTIVITY; CHOLINERGIC NERVE CELL; EMBRYONIC STEM CELL; ENDOTHELIUM CELL; EPITHELIUM CELL; FUNGUS; HUMAN; INFLAMMATION; NEUROTRANSMISSION; NON NEURONAL CHOLINERGIC SYSTEM; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTOZOON; REVIEW; SPONGE (PORIFERA); STIMULUS RESPONSE; WATER FLOW;

ACETYLCHOLINE; ANIMALS; GENE EXPRESSION; HUMANS; INFLAMMATION; NEURONS; RECEPTORS, MUSCARINIC; RECEPTORS, NICOTINIC;

EID: 49449094458     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1038/bjp.2008.185     Document Type: Review

References (173)

1. Abbruscato TJ, Lopez SP, Mark KS, Hawkins BT, Davis TP (2002). Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci 91: 2525-2538.
2. Acevedo M (1994). Effect of acetylcholine on ion transport in sheep tracheal epithelium. Pflugers Arch 427: 543-546.
3. Albaugh G, Bellavance E, Strande L, Heinburger S, Hewitt CW, Alexander JB (2004). Nicotine induces mononuclear leukocyte adhesion and expression of adhesion molecules, VCAM and ICAM, in endothelial cells in vitro. Ann Vasc Surg 18: 302-307.
4. Alexander SPH, Mathie A, Peters JA (2006). Guide to receptors and channels. Br J Pharmacol (Suppl) 147: S85.
5. Allen MJ, Murphey RK (2007). The chemical component of the mixed GF-TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter. Eur J Neurosci 26: 439-445.
6. Anderson AA, Ushakov DS, Ferenczi MA, Mori R, Martin P, Saffell JL (2007). Morphoregulation by acetylcholinesterase in fibroblasts and astrocytes. J Cell Physiol 215: 82-100.
7. Arredondo J, Chernyavsky AI, Jolkovsky DL, Pinkerton KE, Grando SA (2008). Receptor-mediated tobacco toxicity: acceleration of sequential expression of α5 and α7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke. FASEB J 22: 1356-1368.
8. Batra S (1990). Influence of chronic oestrogen treatment on the density of muscarinic cholinergic receptors and calcium channels in the rabbit uterus. J Endocrinol 125: 185-189.
9. Beckel JM, Kanai A, Lee SJ, de Groat WC, Birder LA (2006). Expression of functional nicotinic acetylcholine receptors in rat urinary bladder epithelial cells. Am J Physiol Renal Physiol 290: F103-F110.
10. Bellinger DL, Lorton D, Hamill RW, Felten SY, Felten DL (1993). Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation. Brain Behav Immun 7: 191-204.
11. Blanchet MR, Langlois A, Israël-Assayag E, Beaulieu MJ, Ferland C, Laviolette M et al. (2007). Modulation of eosinophil activation in vitro by a nicotinic receptor agonist. J Leukoc Biol 81: 1245-1251.
12. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR et al. (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405: 458-462.
13. Bruggmann D, Lips KS, Pfeil U, Haberberger RV, Kummer W (2003). Rat arteries contain multiple nicotinic acetylcholine receptor alpha-subunits. Life Sci 72: 2095-2099.
14. Brunn G, Wessler I, Racke K (1995). Mucosa-dependent muscarinic liberation of prostaglandins from rat isolated trachea. Br J Pharmacol 116: 1991-1998.
15. Bschleipfer T, Schukowski K, Weidner W, Grando SA, Schwantes U, Kummer W et al. (2007). Expression and distribution of cholinergic receptors in the human urothelium. Life Sci 80: 2303-2307.
16. Buchli R, Ndoye A, Arredondo J, Webber RJ, Grando SA (2001). Identification and characterization of muscarinic acetylcholine receptor subtypes expressed in human skin melanocytes. Mol Cell Biochem 228: 57-72.
17. Buchli R, Ndoye A, Rodriguez JG, Zia S, Webber RJ, Grando SA (1999). Human skin fibroblasts express m2, m4, and m5 subtypes of muscarinic acetylcholine receptors. J Cell Biochem 74: 264-277.
18. Buhling F, Lieder N, Kuhlmann UC, Waldburg N, Welte T (2007). Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro. Respir Med 101: 2386-2394.
19. Bulloch K, Moore RY (1981). Innervation of the thymus gland by brain stem and spinal cord in mouse and rat. Am J Anat 162: 157-166.
20. Carlisle DL, Hopkins TM, Gaither-Davis A, Silhanek MJ, Luketich JD, Christie NA et al. (2004). Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts. Respir Res 5: 27.
21. Carlisle DL, Liu X, Hopkins TM, Swick MC, Dhir R, Siegfried JM (2007). Nicotine activates cell-signaling pathways through muscle-type and neuronal nicotinic acetylcholine receptors in non-small cell lung cancer cells. Pulm Pharmacol Ther 20: 629-641.
22. Carrasco-Serrano C, Criado M (2004). Glucocorticoid activation of the neuronal nicotinic acetylcholine receptor alpha7 subunit gene: involvement of transcription factor Egr-1. FEBS Lett 566: 247-250.
23. Casanova M, Furlán C, Sterin-Borda L, Borda ES (2006). Muscarinic cholinoceptor activation modulates DNA synthesis and CD40 expression in fibroblast cells. Auton Autacoid Pharmacol 26: 293-301.
24. Cattaneo MG, D'atri F, Vicentini LM (1997). Mechanisms of mitogen-activated protein kinase activation by nicotine in small-cell lung carcinoma cells. Biochem J 328: 499-503.
25. Chernyavsky AI, Arredondo J, Karlsson E, Wessler I, Grando SA (2005). The Ras/Raf-1/MEK1/ERK signaling pathway coupled to integrin expression mediates cholinergic regulation of keratinocyte directional migration. J Biol Chem 280: 39220-39228.
26. Chernyavsky AI, Arredondo J, Marubio LM, Grando SA (2004). Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes. J Cell Sci 117: 5665-5679.
27. Chernyavsky AI, Arredondo J, Vetter DE, Grando SA (2007). Central role of alpha9 acetylcholine receptor in coordinating keratinocyte adhesion and motility at the initiation of epithelialization. Exp Cell Res 313: 3542-3555.
28. Chernyavsky AI, Nguyen VT, Arredondo J, Ndoye A, Zia S, Wess J et al. (2003). The M4 muscarinic receptor-selective effects on keratinocyte crawling locomotion. Life Sci 72: 2069-2073.
29. Cooke JP (2007). Angiogenesis and the role of the endothelial nicotinic acetylcholine receptor. Life Sci 80: 2347-2351.
30. Danielson P, Andersson G, Alfredson H, Forsgren S (2007). Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study. Life Sci 80: 2235-2238.
31. Dasgupta P, Chellappan SP (2006). Nicotine-mediated cell proliferation and angiogenesis: new twists to an old story. Cell Cycle 5: 2324-2328.
32. De Jonge WJ, Ulloa L (2007). The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151: 915-929.
33. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ et al. (2005). Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6: 844-851.
34. Decoursey TE, Chandy KG, Gupta S, Cahalan MD (1987). Mitogen induction of ion channels in murine T lymphocytes. J Gen Physiol 89: 405-420.
35. Dorion G, Israel-Assayag E, Beaulieu MJ, Cormier Y (2005). Effect of 1, 1-dimethylphenyl 1, 4-piperazinium on mouse tracheal smooth muscle responsiveness. Am J Physiol Lung Cell Mol Physiol 288: L1139-L1145.
36. Eglen RM (2006). Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. Auton Autacoid Pharmacol 26: 219-233.
37. Evora PR, Cable DG, Chua YL, Rodrigues AJ, Pearson PJ, Schaff HV (2007). Nitric oxide and prostacyclin-dependent pathways involvement on in vitro induced hypothermia. Cryobiology 54: 106-113.
38. Fritz S, Kunz L, Dimitrijevic N, Grunert R, Heiss C, Mayerhofer A (2002). Muscarinic receptors in human luteinized granulosa cells: activation blocks gap junctions and induces the transcription factor early growth response factor-1. J Clin Endocrinol Metab 87: 1362-1367.
39. Fritz S, Wessler I, Breitling R, Rossmanith W, Ojeda SR, Dissen GA et al. (2001). Expression of muscarinic receptor types in the primate ovary and evidence for nonneuronal acetylcholine synthesis. J Clin Endocrinol Metab 86: 349-354.
40. Fujii T, Yamada S, Watanabe Y, Misawa H, Tajima S, Fujimoto K et al. (1998). Induction of choline acetyltransferase mRNA in human mononuclear leukocytes stimulated by phytohemagglutinin, a T-cell activator. J Neuroimmunol 82: 101-107.
41. Gautam D, Duttaroy A, Cui Y, Han SJ, Deng C, Seeger T et al. (2006). M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes. J Mol Neurosci 30: 157-160.
42. Gautam D, Han SJ, Heard TS, Cui Y, Miller G, Bloodworth L et al. (2005). Cholinergic stimulation of amylase secretion from pancreatic acinar cells studied with muscarinic acetylcholine receptor mutant mice. J Pharmacol Exp Ther 313: 995-1002.
43. Gautam D, Heard TS, Cui Y, Miller G, Bloodworth L, Wess J (2004). Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. Mol Pharmacol 66: 260-267.
44. Goehler LE, Erisir A, Gaykema RP (2006). Neural-immune interface in the rat area postrema. Neuroscience 140: 1415-1434.
45. Gosens R, Dueck G, Gerthoffer WT, Unruh H, Zaagsma J, Meurs H et al. (2007). p42/p44 MAP kinase activation is localized to caveolae-free membrane domains in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 292: L1163-L1172.
46. Gosens R, Zaagsma J, Grootte Bromhaar M, Nelemans A, Meurs H (2004). Acetylcholine: a novel regulator of airway smooth muscle remodelling? Eur J Pharmacol 500: 193-201.
47. Gosens R, Zaagsma J, Meurs H, Halayko AJ (2006). Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res 7: 73.
48. Grando SA (1997). Biological functions of keratinocyte cholinergic receptors. J Investig Dermatol Symp Proc 2: 41-48.
49. Grando SA (2000). Autoimmunity to keratinocyte acetylcholine receptors in pemphigus. Dermatology 201: 290-295.
50. Grando SA (2003). Mucocutaneous cholinergic system is targeted in mustard-induced vesication. Life Sci 72: 2135-2144.
51. Grando SA, Horton RM, Pereira EF, Diethelm-Okita BM, George PM, Albuquerque EX et al. (1995). A nicotinic acetylcholine receptor regulating cell adhesion and motility is expressed in human keratinocytes. J Invest Dermatol 105: 774-781.
52. Grando SA, Kawashima K, Kirkpatrick CJ, Wessler I (2007). Recent progress in understanding the non-neuronal cholinergic system in humans. Life Sci 80: 2181-2185.
53. Grando SA, Kist DA, Qi M, Dahl MV (1993). Human keratinocytes synthesize, secrete, and degrade acetylcholine. J Invest Dermatol 101: 32-36.
54. Grando SA, Pittelkow MR, Schallreuter KU (2006). Adrenergic and cholinergic control in the biology of epidermis: physiological and clinical significance. J Invest Dermatol 126: 1948-1965.
55. Grueb M, Reinthal E, Rohrbach JM, Bartz-Schmidt KU (2006). Muscarinic acetylcholine receptor subtypes in human corneal epithelium and endothelium. Graefes Arch Clin Exp Ophthalmol 244: 1191-1195.
56. Gwilt CR, Donnelly LE, Rogers DF (2007). The non-neuronal cholinergic system in the airways: an unappreciated regulatory role in pulmonary inflammation? Pharmacol Ther 115: 208-222.
57. Haberberger R, Schultheiss G, Diener M (2006). Epithelial muscarinic M1 receptors contribute to carbachol-induced ion secretion in mouse colon. Eur J Pharmacol 530: 229-233.
58. Haberberger RV, Pfeil U, Lips KS, Kummer W (2002). Expression of the high-affinity choline transporter, CHT1, in the neuronal and non-neuronal cholinergic system of human and rat skin. J Invest Dermatol 119: 943-948.
59. Hagforsen E (2007). The cutaneous non-neuronal cholinergic system and smoking related dermatoses: studies of the psoriasis variant palmoplantar pustulosis. Life Sci 80: 2227-2234.
60. Hanna-Mitchell AT, Beckel JM, Barbadora S, Kanai AJ, de Groat WC, Birder LA (2007). Non-neuronal acetylcholine and urinary bladder urothelium. Life Sci 80: 2298-2302.
61. Hasse S, Chernyavsky AI, Grando SA, Paus R (2007). The M4 muscarinic acetylcholine receptor plays a key role in the control of murine hair follicle cycling and pigmentation. Life Sci 80: 2248-2252.
62. Hawkins BT, Egleton RD, Davis TP (2005). Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors. Am J Physiol Heart Circ Physiol 289: H212-H219.
63. Hecker A, Lips K, Pfeil U, Kummer W, Zakrzewics A, Padberg W et al. (2006). Up-regulation of high-affinity choline transporter (CHT1) and choline acetyltransferase (CHAT) gene expression by intravascular leukocytes during acute rejection of renal allografts. Eur Surg Res (Suppl 1) 38: 23.
64. Heeschen C, Chang E, Aicher A, Cooke JP (2006). Endothelial progenitor cells participate in nicotine-mediated angiogenesis. J Am Coll Cardiol 48: 2553-2560.
65. Heeschen C, Weis M, Aicher A, Dimmeler S, Cooke JP (2002). A novel angiogenic pathway mediated by non-neuronal nicotinic acetylcholine receptors. J Clin Invest 110: 527-536.
66. Heeschen C, Weis M, Cooke JP (2003). Nicotine promotes arteriogenesis. J Am Coll Cardiol 41: 489-496.
67. Hirota CL, McKay DM (2006). Cholinergic regulation of epithelial ion transport in the mammalian intestine. Br J Pharmacol 149: 463-479.
68. Horiuchi Y, Kimura R, Kato N, Fujii T, Seki M, Endo T et al. (2003). Evolutional study on acetylcholine expression. Life Sci 72: 1745-1756.
69. Jansen JW, Fleuren-Jakobs AM, De Pont JJ, Bonting SL (1980). Blocking by 2, 4, 6-triaminopyrimidine of increased tight junction permeability induced by acetylcholine in the pancreas. Biochim Biophys Acta 598: 115-126.
70. Jin Z, Gao F, Flagg T, Deng X (2004). Nicotine induces multi-site phosphorylation of Bad in association with suppression of apoptosis. J Biol Chem 279: 23837-23844.
71. Jonsson M, Norrgard O, Forsgren S (2007). Presence of a marked nonneuronal cholinergic system in human colon: study of normal colon and colon in ulcerative colitis. Inflamm Bowel Dis 13: 1347-1356.
72. Kao I, Drachman DB, Price DL (1976). Botulinum toxin: mechanism of presynaptic blockade. Science 193: 1256-1258.
73. Kawashima K, Fujii T (2000). Extraneuronal cholinergic system in lymphocytes. Pharmacol Ther 86: 29-48.
74. Kawashima K, Fujii T (2003). The lymphocytic cholinergic system and its biological function. Life Sci 72: 2101-2109.
75. Kawashima K, Fujii T (2004). Expression of non-neuronal acetylcholine in lymphocytes and its contribution to the regulation of immune function. Front Biosci 9: 2063-2085.
76. Kawashima K, Fujii T, Watanabe Y, Misawa H (1998). Acetylcholine synthesis and muscarinic receptor subtype mRNA expression in T-lymphocytes. Life Sci 62: 1701-1705.
77. Kawashima K, Yoshikawa K, Fujii YX, Moriwaki Y, Misawa H (2007). Expression and function of genes encoding cholinergic components in murine immune cells. Life Sci 80: 2314-2319.
78. Khurana S, Chacon I, Xie G, Yamada M, Wess J, Raufman JP et al. (2004). Vasodilatory effects of cholinergic agonists are greatly diminished in aorta from M3R-/- mice. Eur J Pharmacol 493: 127-132.
79. Kim MH, Kim MO, Heo JS, Kim JS, Han HJ (2008). Acetylcholine inhibits long-term hypoxia-induced apoptosis by suppressing the oxidative stress-mediated MAPKs activation as well as regulation of Bcl-2, c-IAPs, and caspase-3 in mouse embryonic stem cells. Apoptosis 13: 295-304.
80. Kirkpatrick CJ, Bittinger F, Nozadze K, Wessler I (2003). Expression and function of the non-neuronal cholinergic system in endothelial cells. Life Sci 72: 2111-2116.
81. Klapproth H, Racke K, Wessler I (1994). Modulation of the airway smooth muscle tone by mediators released from cultured epithelial cells of rat trachea. Naunyn Schmiedebergs Arch Pharmacol (Suppl) 349: R72.
82. Klapproth H, Racke K, Wessler I (1998). Acetylcholine and nicotine stimulate the release of granulocyte-macrophage colony stimulating factor from cultured human bronchial epithelial cells. Naunyn Schmiedebergs Arch Pharmacol 357: 472-475.
83. Klapproth H, Reinheimer T, Metzen J, Munch M, Bittinger F, Kirkpatrick CJ et al. (1997). Non-neuronal acetylcholine, a signalling molecule synthezised by surface cells of rat and man. Naunyn Schmiedebergs Arch Pharmacol 355: 515-523.
84. Koyama S, Rennard SI, Robbins RA (1992). Acetylcholine stimulates bronchial epithelial cells to release neutrophil and monocyte chemotactic activity. Am J Physiol 262: L466-L471.
85. Kummer W, Wiegand S, Akinci S, Wessler I, Schinkel AH, Wess J et al. (2006). Role of acetylcholine and polyspecific cation transporters in serotonin-induced bronchoconstriction in the mouse. Respir Res 7: 65-72.
86. Kunz L, Roggors C, Mayerhofer A (2007). Ovarian acetylcholine and ovarian KCNQ channels: insights into cellular regulatory systems of steroidogenic granulosa cells. Life Sci 80: 2195-2198.
87. Kurzen H, Berger H, Jager C, Hartschuh W, Naher H, Gratchev A et al. (2004). Phenotypical and molecular profiling of the extraneuronal cholinergic system of the skin. J Invest Dermatol 123: 937-949.
88. Kurzen H, Wessler I, Kirkpatrick CJ, Kawashima K, Grando SA (2007). The non-neuronal cholinergic system of human skin. Horm Metab Res 39: 125-135.
89. Lee SC, Sabath DE, Deutsch C, Prystowsky MB (1986). Increased voltage-gated potassium conductance during interleukin 2-stimulated proliferation of a mouse helper T lymphocyte clone. J Cell Biol 102: 1200-1208.
90. Lips KS, Luhrmann A, Tschernig T, Stoeger T, Alessandrini F, Grau V et al. (2007a). Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse. Life Sci 80: 2263-2269.
91. Lips KS, Pfeil U, Reiners K, Rimasch C, Kuchelmeister K, Braun-Dullaeus RC et al. (2003). Expression of the high-affinity choline transporter CHT1 in rat and human arteries. J Histochem Cytochem 51: 1645-1654.
92. Lips KS, Volk C, Schmitt BM, Pfeil U, Arndt P, Miska D et al. (2005). Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. Am J Respir Cell Mol Biol 33: 79-88.
93. Lips KS, Wunsch J, Zarghooni S, Bschleipfer T, Schukowski K, Weidner W et al. (2007b). Acetylcholine and molecular components of its synthesis and release machinery in the urothelium. Eur Urol 51: 1042-1053.
94. Liu RH, Mizuta M, Matsukura S (2004). The expression and functional role of nicotinic acetylcholine receptors in rat adipocytes. J Pharmacol Exp Ther 310: 52-58.
95. Matthiesen S, Bahulayan A, Holz O, Racke K (2007). MAPK pathway mediates muscarinic receptor-induced human lung fibroblast proliferation. Life Sci 80: 2259-2262.
96. Matthiesen S, Bahulayan A, Kempkens S, Haag S, Fuhrmann M, Stichnote C et al. (2006). Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am J Respir Cell Mol Biol 35: 621-627.
97. Maus AD, Pereira EF, Karachunski PI, Horton RM, Navaneetham D, Macklin K et al. (1998). Human and rodent bronchial epithelial cells express functional nicotinic acetylcholine receptors. Mol Pharmacol 54: 779-788.
98. Mayerhofer A, Fritz S (2002). Ovarian acetylcholine and muscarinic receptors: hints of a novel intrinsic ovarian regulatory system. Microsc Res Tech 59: 503-508.
99. Metzen J, Bittinger F, Kirkpatrick CJ, Kilbinger H, Wessler I (2003). Proliferative effect of acetylcholine on rat trachea epithelial cells is mediated by nicotinic receptors and muscarinic receptors of the M1-subtype. Life Sci 72: 2075-2080.
100. Miao FJ, Benowitz NL, Heller PH, Levine JD (1997b). Contribution of adrenal hormones to nicotine-induced inhibition of synovial plasma extravasation in the rat. Br J Pharmacol 120: 298-304.
101. Miao FJ, Benowitz NL, Levine JD (2001). Endogenous opioids suppress activation of nociceptors by sub-nanomolar nicotine. Br J Pharmacol 133: 23-28.
102. Miao FJ, Jänig W, Levine JD (1997a). Vagal branches involved in inhibition of bradykinin-induced synovial plasma extravasation by intrathecal nicotine and noxious stimulation in the rat. J Physiol 498: 473-481.
103. Milner P, Kirkpatrick KA, Ralevic V, Toothill V, Pearson J, Burnstock G (1990). Endothelial cells cultured from human umbilical vein release ATP, substance P and acetylcholine in response to increased flow. Proc Biol Sci 241: 245-248.
104. Moser N, Mechawar N, Jones I, Gochberg-Sarver A, Orr-Urtreger A, Plomann M et al. (2007). Evaluating the suitability of nicotinic acetylcholine receptor antibodies for standard immunodetection procedures. J Neurochem 102: 479-492.
105. Nance DM, Hopkins DA, Bieger D (1987). Re-investigation of the innervation of the thymus gland in mice and rats. Brain Behav Immun 1: 134-147.
106. Nance DM, Sanders VM (2007). Autonomic innervation and regulation of the immune system (1987-2007). Brain Behav Immun 21: 736-745.
107. Neumann S, Razen M, Habermehl P, Meyer CU, Zepp F, Kirkpatrick CJ et al. (2007). The non-neuronal cholinergic system in peripheral blood cells: effects of nicotinic and muscarinic receptor antagonists on phagocytosis, respiratory burst and migration. Life Sci 80: 2361-2364.
108. Nguyen VT, Hall LL, Gallacher G, Ndoye A, Jolkovsky DL, Webber RJ et al. (2000). Choline acetyltransferase, acetylcholinesterase, and nicotinic acetylcholine receptors of human gingival and esophageal epithelia. J Dent Res 79: 939-949.
109. Oda Y (1999). Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int 49: 921-937.
110. Ogawa H, Fujii T, Watanabe Y, Kawashima K (2003). Expression of multiple mRNA species for choline acetyltransferase in human T-lymphocytes. Life Sci 72: 2127-2130.
111. Ohtani M, Oka T, Badyuk M, Xiao Y, Kellar KJ, Daly JW (2006). Mouse beta-TC6 insulinoma cells: high expression of functional alpha3-beta4 nicotinic receptors mediating membrane potential, intracellular calcium, and insulin release. Mol Pharmacol 69: 899-907.
112. Olubadewo JO, Rama Sastry BV (1978). Human placental cholinergic system: stimulation-secretion coupling for release of acetylcholine from isolated placental villus. J Pharmacol Exp Ther 204: 433-445.
113. Pahl A, Bauhofer A, Petzold U, Cnota PJ, Maus J, Brune K et al. (2006). Synergistic effects of the anti-cholinergic R, R-glycopyrrolate with anti-inflammatory drugs. Biochem Pharmacol 72: 1690-1696.
114. Paraoanu LE, Steinert G, Koehler A, Wessler I, Layer PG (2007). Expression and possible functions of the cholinergic system in a murine embryonic stem cell line. Life Sci 80: 2375-2379.
115. Pavlov VA, Tracey KJ (2005). The cholinergic anti-inflammatory pathway. Brain Behav Immun 19: 493-499.
116. Pfeil U, Lips KS, Eberling L, Grau V, Haberberger RV, Kummer W (2003). Expression of the high-affinity choline transporter, CHT1, in the rat trachea. Am J Respir Cell Mol Biol 28: 473-477.
117. Plummer III HK, Dhar M, Schuller HM (2005). Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells. Respir Res 6: 29.
118. Profita M, Bonanno A, Siena L, Ferraro M, Montalbano AM, Pompeo F et al. (2008). Acetylcholine mediates the release of IL-8 in human bronchial epithelial cells by a NFkB/ERK-dependent mechanism. Eur J Pharmacol 582: 145-153.
119. Profita M, Giorgi RD, Sala A, Bonanno A, Riccobono L, Mirabella F et al. (2005). Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD patients. Allergy 60: 1361-1369.
120. Proskocil BJ, Sekhon HS, Jia Y, Savchenko V, Blakely RD, Lindstrom J et al. (2004). Acetylcholine is an autocrine or paracrine hormone synthesized and secreted by airway bronchial epithelial cells. Endocrinology 145: 2498-2506.
121. Qu J, Zhou X, Xie R, Zhang L, Hu D, Li H et al. (2006). The presence of m1 to m5 receptors in human sclera: evidence of the sclera as a potential site of action for muscarinic receptor antagonists. Curr Eye Res 31: 587-597.
122. Racké K, Haag S, Jürgens KU, Warnken M (2008). Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Naunyn Schmiedebergs Arch Pharmacol (Suppl) 377: 17.
123. Racké K, Juergens UR, Matthiesen S (2006). Control by cholinergic mechanisms. Eur J Pharmacol 533: 57-68.
124. Raufman JP, Cheng K, Zimniak P (2003). Activation of muscarinic receptor signaling by bile acids: physiological and medical implications. Dig Dis Sci 48: 1431-1444.
125. 2+ response. J Immunol 179: 2889-2898.
126. Reinheimer T, Bernedo P, Klapproth H, Oelert H, Zeiske B, Racke K et al. (1996). Acetylcholine in isolated airways of rat, guinea pig, and human: species differences in role of airway mucosa. Am J Physiol 270: L722-L728.
127. Reinheimer T, Mohlig T, Zimmermann S, Hohle KD, Wessler I (2000). Muscarinic control of histamine release from airways. Inhibitory M1-receptors in human bronchi but absence in rat trachea. Am J Respir Crit Care Med 162: 534-538.
128. Richardson CE, Morgan JM, Jasani B, Green JT, Rhodes J, Williams GT et al. (2003). Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis. QJM 96: 57-65.
129. Roman J, Ritzenthaler JD, Gil-Acosta A, Rivera HN, Roser-Page S (2004). Nicotine and fibronectin expression in lung fibroblasts: implications for tobacco-related lung tissue remodeling. FASEB J 18: 1436-1438.
130. Romano SJ, Corriveau RA, Schwarz RI, Berg DK (1997). Expression of the nicotinic receptor alpha 7 gene in tendon and periosteum during early development. J Neurochem 68: 640-648.
131. Santos SC, Vala I, Miguel C, Barata JT, Garção P, Agostinho P et al. (2007). Expression and subcellular localization of a novel nuclear acetylcholinesterase protein. J Biol Chem 282: 25597-25603.
132. Sastry BV, Sadavongvivad C (1978). Cholinergic systems in non-nervous tissues. Pharmacol Rev 30: 65-132.
133. Schlereth T, Birklein F, an Haack K, Schiffmann S, Kilbinger H, Kirkpatrick CJ et al. (2006). In vivo release of non-neuronal acetylcholine from the human skin as measured by dermal microdialysis: effect of botulinum toxin. Br J Pharmacol 147: 183-187.
134. Scott A (1962). Acetylcholine in normal and diseased skin. Br J Dermatol 74: 317-322.
135. Sekhon HS, Keller JA, Proskocil BJ, Martin EL, Spindel ER (2002). Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung. Association with alpha7 nicotinic acetylcholine receptors. Am J Respir Cell Mol Biol 26: 31-41.
136. Sekhon HS, Song P, Jia Y, Lindstrom J, Spindel ER (2005). Expression of lynx1 in developing lung and its modulation by prenatal nicotine exposure. Cell Tissue Res 320: 287-297.
137. Serobyan N, Jagannathan S, Orlovskaya I, Schraufstatter I, Skok M, Loring J et al. (2007). The cholinergic system is involved in regulation of the development of the hematopoietic system. Life Sci 80: 2352-2360.
138. Shytle RD, Mori T, Townsend K, Vendrame M, Sun N, Zeng J et al. (2004). Cholinergic modulation of microglial activation by alpha 7 nicotinic receptors. J Neurochem 89: 337-343.
139. Skok MV, Grailhe R, Agenes F, Changeux JP (2007). The role of nicotinic receptors in B-lymphocyte development and activation. Life Sci 80: 2334-2336.
140. Song P, Sekhon HS, Lu A, Arredondo J, Sauer D, Gravett C et al. (2007). M3 muscarinic receptor antagonists inhibit small cell lung carcinoma growth and mitogen-activated protein kinase phosphorylation induced by acetylcholine secretion. Cancer Res 67: 3936-3944.
141. Song P, Sekhon HS, Proskocil B, Blusztajn JK, Mark GP, Spindel ER (2003). Synthesis of acetylcholine by lung cancer. Life Sci 72: 2159-2168.
142. Strassheim D, May LG, Varker KA, Puhl HL, Phelps SH, Porter RA et al. (1999). M3 muscarinic acetylcholine receptors regulate cytoplasmic myosin by a process involving RhoA and requiring conventional protein kinase C isoforms. J Biol Chem 274: 18675-18685.
143. Tournier JM, Maouche K, Coraux C, Zahm JM, Cloez-Tayarani I, Nawrocki-Raby B et al. (2006). Alpha3alpha5beta2-nicotinic acetylcholine receptor contributes to the wound repair of the respiratory epithelium by modulating intracellular calcium in migrating cells. Am J Pathol 168: 55-68.
144. Tracey KJ (2002). The inflammatory reflex. Nature 420: 853-859.
145. Tracey WR, Peach MJ (1992). Differential muscarinic receptor mRNA expression by freshly isolated and cultured bovine aortic endothelial cells. Circ Res 70: 234-240.
146. Trombino S, Cesario A, Margaritora S, Granone P, Motta G, Falugi C et al. (2004). Alpha7-nicotinic acetylcholine receptors affect growth regulation of human mesothelioma cells: role of mitogen-activated protein kinase pathway. Cancer Res 64: 135-145.
147. Tsai CH, Yeh HI, Tian TY, Lee YN, Lu CS, Ko YS (2004). Downregulating effect of nicotine on connexin43 gap junctions in human umbilical vein endothelial cells is attenuated by statins. Eur J Cell Biol 82: 589-595.
148. Ueda F, Ban K, Ishima T (1995). Irsogladine activates gap-junctional intercellular communication through M1 muscarinic acetylcholine receptor. J Pharmacol Exp Ther 274: 815-819.
149. Valera S, Ballivet M, Bertrand D (1992). Progesterone modulates a neuronal nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 89: 9949-9953.
150. Walch L, Brink C, Norel X (2001). The muscarinic receptor subtypes in human blood vessels. Therapie 56: 223-226.
151. Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S et al. (2003). Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421: 384-388.
152. Wang Y, Pereira EF, Maus AD, Ostlie NS, Navaneetham D, Lei S et al. (2001). Human bronchial epithelial and endothelial cells express alpha7 nicotinic acetylcholine receptors. Mol Pharmacol 60: 1201-1209.
153. Wang Y, Wang L, Ai X, Zhao J, Hao X, Lu Y et al. (2004). Nicotine could augment adhesion molecule expression in human endothelial cells through macrophages secreting TNF-alpha, IL-1beta. Int Immunopharmacol 4: 1675-1686.
154. Wang Y, Wang Z, Zhou Y, Liu L, Zhao Y, Yao C et al. (2006). Nicotine stimulates adhesion molecular expression via calcium influx and mitogen-activated protein kinases in human endothelial cells. Int J Biochem Cell Biol 38: 170-182.
155. Wessler I, Bittinger F, Kamin W, Zepp F, Meyer E, Schad A et al. (2007a). Dysfunction of the non-neuronal cholinergic system in the airways and blood cells of patients with cystic fibrosis. Life Sci 80: 2253-2258.
156. Wessler I, Deutsch C, Brockerhoff P, Bittinger F, Kirkpatrick CJ, Kilbinger H (2001d). Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters. Br J Pharmacol 134: 951-956.
157. Wessler I, Holper B, Kortsik C, Buhl R, Kilbinger H, Kirkpatrick CJ (2007b). Dysfunctional inhibitory muscarinic receptors mediate enhanced histamine release in isolated human bronchi. Life Sci 80: 2294-2297.
158. Wessler I, Kilbinger H, Bittinger F, Kirkpatrick CJ (2001a). The biological role of non-neuronal acetylcholine in plants and humans. Jpn J Pharmacol 85: 2-10.
159. Wessler I, Kilbinger H, Bittinger F, Unger R, Kirkpatrick CJ (2003a). The non-neuronal cholinergic system in humans: expression, function and pathophysiology. Life Sci 72: 2055-2061.
160. Wessler I, Kirkpatrick CJ (2001a). The non-neuronal cholinergic system: an emerging drug target in the airways. Pulm Pharmacol Ther 14: 423-434.
161. Wessler I, Kirkpatrick CJ (2001b). Role of non-neuronal and neuronal acetylcholine in the airways. In: Zaagsma J, Meurs H, Roffel AF (eds). Musacrinic Receptors in the Airways. Birkhäuser Verlag: Basel, Boston, Berlin. pp 25-62.
162. Wessler I, Kirkpatrick CJ, Racke K (1998). Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans. Pharmacol Ther 77: 59-79.
163. Wessler I, Kirkpatrick CJ, Racke K (1999). The cholinergic 'pitfall': acetylcholine, a universal cell molecule in biological systems, including humans. Clin Exp Pharmacol Physiol 26: 198-205.
164. Wessler I, Panter H, Bittinger F, Kriegsmann J, Kirkpatrick CJ, Kawashima K et al. (2001c). Subcellular location of choline acetyltransferase (ChAT) and acetylcholine (ACh) in human placenta. Naunyn Schmiedebergs Arch Pharmacol (Suppl) 363: R23.
165. Wessler I, Reinheimer T, Kilbinger H, Bittinger F, Kirkpatrick CJ, Saloga J et al. (2003b). Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis. Life Sci 72: 2169-2172.
166. Wessler I, Roth E, Schwarze S, Weikel W, Bittinger F, Kirkpatrick CJ et al. (2001b). Release of non-neuronal acetylcholine from the human placenta: difference to neuronal acetylcholine. Naunyn Schmiedebergs Arch Pharmacol 364: 205-212.
167. West KA, Brognard J, Clark AS, Linnoila IR, Yang X, Swain SM et al. (2003). Rapid Akt activation by nicotine and a tobacco carcinogen modulates the phenotype of normal human airway epithelial cells. J Clin Invest 111: 81-90.
168. Xie G, Drachenberg C, Yamada M, Wess J, Raufman JP (2005). Cholinergic agonist-induced pepsinogen secretion from murine gastric chief cells is mediated by M1 and M3 muscarinic receptors. Am J Physiol Gastrointest Liver Physiol 289: G521-G529.
169. Yamada M, Lamping KG, Duttaroy A, Zhang W, Cui Y, Bymaster FP et al. (2001). Cholinergic dilation of cerebral blood vessels is abolished in M(5) muscarinic acetylcholine receptor knockout mice. Proc Natl Acad Sci USA 98: 14096-14101.
170. Yoshikawa H, Hellstrom-Lindahl E, Grill V (2005). Evidence for functional nicotinic receptors on pancreatic beta cells. Metabolism 54: 247-254.
171. Zarghooni S, Wunsch J, Bodenbenner M, Bruggmann D, Grando SA, Schwantes U et al. (2007). Expression of muscarinic and nicotinic acetylcholine receptors in the mouse urothelium. Life Sci 80: 2308-2313.
172. Zia S, Ndoye A, Nguyen VT, Grando SA (1997). Nicotine enhances expression of the alpha 3, alpha 4, alpha 5, and alpha 7 nicotinic receptors modulating calcium metabolism and regulating adhesion and motility of respiratory epithelial cells. Res Commun Mol Pathol Pharmacol 97: 243-262.
173. Zimring JC, Kapp LM, Yamada M, Wess J, Kapp JA (2005). Regulation of CD8+ cytolytic T lymphocyte differentiation by a cholinergic pathway. J Neuroimmunol 164: 66-75.