Bladder Outlet Obstruction Mediates Muscarinic Acetylcholine Receptor Expression in the Urothelial Layer

Abstract

Bladder outlet obstruction (BOO) is an important condition which occurs primarily in older men due to the prevalence of benign prostatic hyperplasia (BPH). BPH costs four billion dollars annually in healthcare expenditures in the US alone. BOO induces inflammation in the bladder leading to bladder epithelial (urothelial) layer reorganization and eventually to fibrosis and irreversible bladder dysfunction. Recently Dr. J. Todd Purves’ lab has discovered a critical role for a family of supramolecular complexes called inflammasomes in the induction of this inflammation, specifically the NLRP3 inflammasome. However, it is not known how these inflammasomes influence the population of cell surface receptors in the urothelium. Muscarinic acetylcholine receptors (mAChRs) in the urothelium have been specifically implicated in inducing irrative bladder symptoms such as increased frequency and voiding trouble. To gain insight into this phenomenon, changes in the expression level of several critical cell surface receptors in the urothelium of a rat model of BOO were measured in the presence and absence of NLRP3 inflammasome inhibition. After quantification of receptor expression levels with flow cytometry and immunofluorescence microscopy, BOO was discovered to have direct effects on mAChR expression, through a physiological pathway demonstrated to be mediated by NLRP3 inflammasome activation. The discovery of this relationship moves the field one step closer to understanding ways in which the irrative symptoms associated with BPH and BOO may be alleviated.