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

Abstract

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.

Relationship between lower urinary tract symptoms and urinary ATP in patients with benign prostatic hyperplasia or overactive bladder

“…It is known that bladder epithelial cells express both muscarinic and alpha-1 adrenergic receptors, that these cells produce acetylcholine and ATP, and that afferent nerve terminals in the bladder express muscarinic and purinergic receptors (2,20). Therefore, acetylcholine produced by bladder epithelial cells may activate epithelial cells in an autocrine fashion via their muscarinic receptors.…”

“…These antagonists improve both urinary voiding disorders and urinary collecting disorders, while coadministration of the alpha-1 adrenergic receptor antagonist and the anti-muscarinic agent is more effective for controlling overactive bladder (OAB) in BPH patients (3). Anti-muscarinic agents are known to inhibit bladder smooth muscle contraction, and may possibly also block the effects of muscarinic receptors on bladder epithelial cells (12,20). Bladder epithelial cells exhibit a number of properties similar to those of neurons (nociceptors/mechanoreceptors), and both types of cells share several signal transduction mechanisms to detect physiological stimuli.…”

Detrusor myocyte activity and afferent signaling

“…Yoshida et al 67,68 demonstrated that there is a basal ACh release in human detrusor muscle. This release was resistant to TTX, and considerably reduced when the urothelium was removed, suggesting that the released ACh was of nonneuronal origin and, at least partly, generated by the urothelium.…”

Basic and Clinical Aspects of Non-neuronal Acetylcholine: Overview of Non-neuronal Cholinergic Systems and Their Biological Significance

“…The expression of a non-neuronal cholinergic system in urinary bladder is reviewed in this issue by Yoshida et al (49). Briefly, they observed strong ChAT-positive immunostaining in the urothelial and suburothelial regions of the human urinary bladder (50).…”