Acetylcholine and the alpha 7 nicotinic receptor: a potential therapeutic target for the treatment of periodontal disease?

Abstract

Objectives-The aim of this review is to examine the evidence for a functional cholinergic system operating within the periodontium and determine the evidence for its role in periodontal immunity.Introduction-Acetylcholine can influence the immune system via the 'cholinergic antiinflammatory pathway'. This pathway is mediated by the vagus nerve which releases acetylcholine to interact with the 7 subunit of the nicotinic acetylcholine receptor ( 7nAChR) on proximate immuno-regulatory cells. Activation of the 7nAChR on these cells leads to downregulated expression of pro-inflammatory mediators and thus regulates localised inflammatory responses. The role of the vagus nerve in periodontal pathophysiology is currently unknown. However, non-neuronal cells can also release acetylcholine and express the 7nAChR; these include keratinocytes, fibroblasts, T cells, B cells and macrophages. Therefore, by both autocrine and paracrine methods non-neuronal acetylcholine can also be hypothesised to modulate the localised immune response.

Clinical associations between acetylcholine levels and cholinesterase activity in saliva and gingival crevicular fluid and periodontal diseases

“…Furthermore, oral keratinocytes have been found to release ACh in response to stimulation by Porphyromonas gingivalis and the α7nAChR on oral keratinocytes has been demonstrated to downregulate P. gingivalis induced expression of IL‐8 (CXCL8) (Macpherson et al., ). The evidence therefore suggests that ACh can modulate innate immune responses within the oral mucosa and subsequently the pathogenesis of periodontal diseases (Zoheir et al., ).…”

“…The oral mucosa can be defined as having a non-neuronal cholinergic system (Arredondo et al, 2003;Macpherson et al, 2014;Nguyen et al, 2000;Zoheir, Lappin, & Nile, 2012) due to the fact it expresses ChAT, acetylcholine receptors and cholinesterases (Rana et al, 2010;Wessler & Kirkpatrick, 2008). Roles for non-neuronal ACh within mucosal tissues include; cell proliferation and differentiation, cytoskeletal organization, cell-cell contact, maintenance of effective barrier functions, controlling ion and water movements and modulation of immune responses Wessler & Kirkpatrick, 2008).…”

Research tool: validation of floxed α7 nicotinic acetylcholine receptor conditional knockout mice using in vitro and in vivo approaches

“…As such, α7 nAChRs have been implicated in a variety of biological functions and are considered a prominent therapeutic target in several disease states (Gallowitsch‐Puerta & Tracey, ; Zoheir et al . ; Wallace & Bertrand, ; Young & Geyer, ). Therefore, the ability to control α7 nAChR expression in developmental and cell‐specific manners is crucial to understanding the various roles α7 nAChRs play.…”

“…Alpha7 (α7) nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the peripheral and central nervous systems as well as the immune system and a variety of peripheral tissues (Seguela et al 1993;Dominguez del Toro et al 1994;Rubboli et al 1994a,b;Drago et al 2003). As such, α7 nAChRs have been implicated in a variety of biological functions and are considered a prominent therapeutic target in several disease states (Gallowitsch-Puerta & Tracey, 2005;Zoheir et al 2012;Wallace & Bertrand, 2013;Young & Geyer, 2013). Therefore, the ability to control α7 nAChR expression in developmental and cell-specific manners is crucial to understanding the various roles α7 nAChRs play.…”

Cholinergic signalling mechanisms and early implant healing phases in healthy versus generalized aggressive periodontitis patients: A prospective, case–control study

“…Cholinergic mechanisms exist in the periodontium, and acetylcholine (ACh) has been found to play important roles in both periodontal health and disease (Arredondo et al, ; Nguyen et al, ; Zoheir, Lappin, & Nile, ). ACh is synthesized by cells of the periodontium expressing choline acetyltransferase (ChAT) from acetyl COA and choline (Wessler & Kirkpatrick, ).…”