Non-neuronal cholinergic system in human bladder urothelium

Objectives To evaluate the non-neuronal cholinergic system in the isolated human bladder. Recently, several reports have demonstrated that non-nerve-evoked acetylcholine (ACh) release may contribute to various pathophysiologic conditions. Methods Human bladders were obtained from 15 patients. Bladder strips with or without urothelium were suspended in an organ bath filled with Krebs-Henseleit solution. ACh release was measured using microdialysis and high-performance liquid chromatography. The contribution of urothelium to non-nerve-evoked ACh release was tested, and the effects of age and elevation of the resting tension (0 to 40 mN) on ACh release were also evaluated. Furthermore, choline acetyltransferase (ChAT) immunohistochemical staining of bladder was performed. Results Immunohistochemistry showed marked ChAT-positive staining in the urothelium and suburothelial region. Tetrodotoxin-insensitive non-nerve-evoked ACh release occurred and was significantly greater in strips with than without urothelium. The non-nerve-evoked ACh release from strips with urothelium increased with age, and the positive correlation between age and release was significant. Stretching of the strips caused increases in non-nerve-evoked ACh release that was significantly greater in strips with than without urothelium. The stretch-induced release of non-nerve-evoked ACh increased with age. Conclusions These data have demonstrated that a non-neuronal cholinergic system is present in the human bladder and that the urothelium/suburothelium partially releases ACh. We found a significant age-related and stretch-induced increase in non-nerve-evoked ACh release. This suggests that the non-neuronal cholinergic system may contribute to the physiology and pathophysiology of human bladder function.