The Non-neuronal Cholinergic System: an Emerging Drug Target in the Airways

Wessler, Ignaz; Kirkpatrick, Charles James

doi:10.1006/pupt.2001.0313

Cited by 167 publications

(116 citation statements)

References 97 publications

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“…In addition, tiotropium bromide also partially prevented MUC5AC expression by airway goblet cells, and tended to reduce goblet cell number in saline-and OVA-challenged animals. Innervation of airway epithelial cells, including goblet cells, varies between species [34]; however, these cells are known to express the acetylcholine-synthesising enzyme choline acetyltransferase, transporter molecules for the excretion of acetylcholine and acetylcholine itself [35][36][37][38]. It is unclear whether the acetylcholine involved in the allergen-induced mucous differentiation of the airway epithelium is neuronal or non-neuronal in origin.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison

Bos¹,

Gosens²,

Zuidhof³

et al. 2007

European Respiratory Journal

193

166

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Chronic inflammation in asthma and chronic obstructive pulmonary disease drives pathological structural remodelling of the airways. Using tiotropium bromide, acetylcholine was recently identified as playing a major regulatory role in airway smooth muscle remodelling in a guinea pig model of ongoing allergic asthma. The aim of the present study was to investigate other aspects of airway remodelling and to compare the effectiveness of tiotropium to the glucocorticosteroid budesonide.Ovalbumin-sensitised guinea pigs were challenged for 12 weeks with aerosolised ovalbumin. The ovalbumin induced airway smooth muscle thickening, hypercontractility of tracheal smooth muscle, increased pulmonary contractile protein (smooth-muscle myosin) abundance, mucous gland hypertrophy, an increase in mucin 5 subtypes A and C (MUC5AC)-positive goblet cell numbers and eosinophilia. It was reported previously that treatment with tiotropium inhibits airway smooth muscle thickening and contractile protein expression, and prevents tracheal hypercontractility. This study demonstrates that tiotropium also fully prevented allergen-induced mucous gland hypertrophy, and partially reduced the increase in MUC5AC-positive goblet cell numbers and eosinophil infiltration. Treatment with budesonide also prevented airway smooth muscle thickening, contractile protein expression, tracheal hypercontractility and mucous gland hypertrophy, and partially reduced MUC5AC-positive goblet cell numbers and eosinophilia.This study demonstrates that tiotropium and budesonide are similarly effective in inhibiting several aspects of airway remodelling, providing further evidence that the beneficial effects of tiotropium bromide might exceed those of bronchodilation.

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Section: Discussionmentioning

confidence: 99%

Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison

Bos¹,

Gosens²,

Zuidhof³

et al. 2007

European Respiratory Journal

193

166

View full text Add to dashboard Cite

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“…In the present experiment, in bladder strips without urothelium, a small amount of basal ACh release was observed, and stretching the strips also caused an increase in ACh release, although this was significantly lower than the stretch-induced ACh release from strips with urothelium. It has been reported that smooth muscle cells have a non-neuronal cholinergic system (20). Furthermore, it is possible that removal of urothelium may remove some cellular components located in the suburothelial layer, such as myofibroblasts and interstitial pacemaker cells.…”

Section: Effects Of Urothelium and Bladder Stretch On Nonneuronal Achmentioning

confidence: 99%

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Expression of Non-neuronal Acetylcholine in Urothelium and Its Clinical Significance

et al. 2008

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Abstract.Recently, several reports demonstrate that non-neuronal acetylcholine (ACh) release may contribute to various pathophysiological conditions. In this review, we presented our experiments designed to evaluate the non-neuronal cholinergic system in human bladder. After insertion of the microdialysis probe, human bladder strips were suspended in an organ bath filled with Krebs-Henseleit solution, and Ringer solution was perfused into the probe. ACh release was measured by microdialysis and HPLC. The contribution of urothelium and the effects of age and stretch of bladder strips on non-neuronal ACh release were evaluated. Choline acetyltransferase (ChAT) immunohistochemical staining of bladder was also performed. Immunohistochemistry showed marked ChAT-positive staining in the urothelium. There was tetrodotoxininsensitive non-neuronal ACh release and this was significantly higher in strips with urothelium than in strips without urothelium. The non-neuronal ACh release was increased with age. Stretch of bladder strips caused increases in non-neuronal ACh release. The stretch-induced release of non-neuronal ACh was increased with age. Our data demonstrate that there is a non-neuronal cholinergic system in human bladder and that urothelium contributes to non-neuronal ACh release. There was significant age-related and stretch-induced increase in non-neuronal ACh release. It is suggested that the non-neuronal cholinergic system may contribute to the physiology and pathophysiology of human bladder. We also discussed the clinical significance of the nonneuronal cholinergic system in human bladder.

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“…In the airways, for instance, the great majority of cells express the components of NNCS and it is documented that a substantial increase on ACh levels triggers the release of proinflammatory effectors [34]. In addition, the excitability of airway mast cells can be powerfully inhibited by acetylcholine [35].…”

Section: Non-neuronal Cholinergic System (Nncs)mentioning

confidence: 99%