The Alpha7 Nicotinic Acetylcholine Receptor As a Pharmacological Target for Inflammation

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2007 May 16

PMID 17502850

Citations 276

Authors

W J de Jonge

L Ulloa

Affiliations

Soon will be listed here.

Abstract

The physiological regulation of the immune system encompasses comprehensive anti-inflammatory mechanisms that can be harnessed for the treatment of infectious and inflammatory disorders. Recent studies indicate that the vagal nerve, involved in control of heart rate, hormone secretion and gastrointestinal motility, is also an immunomodulator. In experimental models of inflammatory diseases, vagal nerve stimulation attenuates the production of proinflammatory cytokines and inhibits the inflammatory process. Acetylcholine, the principal neurotransmitter of the vagal nerve, controls immune cell functions via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). From a pharmacological perspective, nicotinic agonists are more efficient than acetylcholine at inhibiting the inflammatory signaling and the production of proinflammatory cytokines. This 'nicotinic anti-inflammatory pathway' may have clinical implications as treatment with nicotinic agonists can modulate the production of proinflammatory cytokines from immune cells. Nicotine has been tested in clinical trials as a treatment for inflammatory diseases such as ulcerative colitis, but the therapeutic potential of this mechanism is limited by the collateral toxicity of nicotine. Here, we review the recent advances that support the design of more specific receptor-selective nicotinic agonists that have anti-inflammatory effects while eluding its collateral toxicity.

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References

Driessler F, Venstrom K, Sabat R, Asadullah K, Schottelius A . Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappaB activity: a role for p50. Clin Exp Immunol. 2003; 135(1):64-73. PMC: 1808913. DOI: 10.1111/j.1365-2249.2004.02342.x. View

Hamano R, Takahashi H, Iwagaki H, Yoshino T, Nishibori M, Tanaka N . Stimulation of alpha7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes. Shock. 2006; 26(4):358-64. DOI: 10.1097/01.shk.0000228168.86845.60. View

Feldmann M . Development of anti-TNF therapy for rheumatoid arthritis. Nat Rev Immunol. 2002; 2(5):364-71. DOI: 10.1038/nri802. View

Villiger Y, Szanto I, Jaconi S, Blanchet C, Buisson B, Krause K . Expression of an alpha7 duplicate nicotinic acetylcholine receptor-related protein in human leukocytes. J Neuroimmunol. 2002; 126(1-2):86-98. DOI: 10.1016/s0165-5728(02)00057-7. View

Khiroug S, Harkness P, Lamb P, Sudweeks S, Khiroug L, Millar N . Rat nicotinic ACh receptor alpha7 and beta2 subunits co-assemble to form functional heteromeric nicotinic receptor channels. J Physiol. 2002; 540(Pt 2):425-34. PMC: 2290261. DOI: 10.1113/jphysiol.2001.013847. View

Davies B, Hoss W, Lin J, Lionetti F . Evidence for a noncholinergic nicotine receptor on human phagocytic leukocytes. Mol Cell Biochem. 1982; 44(1):23-31. DOI: 10.1007/BF00573842. View

Stead R, Colley E, Wang B, Partosoedarso E, Lin J, Stanisz A . Vagal influences over mast cells. Auton Neurosci. 2006; 125(1-2):53-61. DOI: 10.1016/j.autneu.2006.01.002. View

Meyer E, Kuryatov A, Gerzanich V, Lindstrom J, Papke R . Analysis of 3-(4-hydroxy, 2-Methoxybenzylidene)anabaseine selectivity and activity at human and rat alpha-7 nicotinic receptors. J Pharmacol Exp Ther. 1998; 287(3):918-25. View

Rutgeerts P, Van Assche G, Vermeire S . Review article: Infliximab therapy for inflammatory bowel disease--seven years on. Aliment Pharmacol Ther. 2006; 23(4):451-63. DOI: 10.1111/j.1365-2036.2006.02786.x. View

10.

Luyer M, Greve J, Hadfoune M, Jacobs J, Dejong C, Buurman W . Nutritional stimulation of cholecystokinin receptors inhibits inflammation via the vagus nerve. J Exp Med. 2005; 202(8):1023-9. PMC: 2213207. DOI: 10.1084/jem.20042397. View

11.

Hellstrom-Lindahl E . Modulation of beta-amyloid precursor protein processing and tau phosphorylation by acetylcholine receptors. Eur J Pharmacol. 2000; 393(1-3):255-63. DOI: 10.1016/s0014-2999(00)00028-5. View

12.

Nouri-Shirazi M, Guinet E . Evidence for the immunosuppressive role of nicotine on human dendritic cell functions. Immunology. 2003; 109(3):365-73. PMC: 1782971. DOI: 10.1046/j.1365-2567.2003.01655.x. View

13.

Bouzat C, Gumilar F, Spitzmaul G, Wang H, Rayes D, Hansen S . Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel. Nature. 2004; 430(7002):896-900. DOI: 10.1038/nature02753. View

14.

Iho S, Tanaka Y, Takauji R, Kobayashi C, Muramatsu I, Iwasaki H . Nicotine induces human neutrophils to produce IL-8 through the generation of peroxynitrite and subsequent activation of NF-kappaB. J Leukoc Biol. 2003; 74(5):942-51. DOI: 10.1189/jlb.1202626. View

15.

Akk G, Steinbach J . Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site. J Neurosci. 2005; 25(8):1992-2001. PMC: 6726061. DOI: 10.1523/JNEUROSCI.4985-04.2005. View

16.

Rice T, Bernard G . Therapeutic intervention and targets for sepsis. Annu Rev Med. 2005; 56:225-48. DOI: 10.1146/annurev.med.56.082103.104356. View

17.

Suzuki T, Hide I, Matsubara A, Hama C, Harada K, Miyano K . Microglial alpha7 nicotinic acetylcholine receptors drive a phospholipase C/IP3 pathway and modulate the cell activation toward a neuroprotective role. J Neurosci Res. 2006; 83(8):1461-70. DOI: 10.1002/jnr.20850. View

18.

Aicher A, Heeschen C, Mohaupt M, Cooke J, Zeiher A, Dimmeler S . Nicotine strongly activates dendritic cell-mediated adaptive immunity: potential role for progression of atherosclerotic lesions. Circulation. 2003; 107(4):604-11. DOI: 10.1161/01.cir.0000047279.42427.6d. View

19.

Shaw S, Bencherif M, Marrero M . Janus kinase 2, an early target of alpha 7 nicotinic acetylcholine receptor-mediated neuroprotection against Abeta-(1-42) amyloid. J Biol Chem. 2002; 277(47):44920-4. DOI: 10.1074/jbc.M204610200. View

20.

Rubin D, Hanauer S . Smoking and inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2000; 12(8):855-62. DOI: 10.1097/00042737-200012080-00004. View