Antimuscarinic actions on bladder urothelium and lamina propria contractions are similar to those observed in detrusor smooth muscle preparations

Abstract

AbstractObjectivesAntimuscarinic medications are the first‐line treatments for overactive bladder, the most common form of bladder dysfunction. Their primary action is thought to block detrusor muscarinic receptors. It is unclear, however, if these therapeutics have actions on other tissues within the lower urinary tract. This study assessed whether clinical antimuscarinics have a functional impact on urothelium with lamina propria (U&LP) tissue.MethodsStrips of porcine detrusor and U&LP were mounted in carbogen‐gassed Krebs‐bicarbonate solution at 37°C. The tissues were paired with carbachol‐response curves performed in the absence or presence of each antimuscarinic. pEC50 values for each curve were analyzed and estimated affinities calculated.ResultsBoth detrusor and U&LP tissues contracted with muscarinic receptor stimulation, which was inhibited by commonly used antimuscarinics. In detrusor samples (p < 0.001 for all), right parallel shifts from the control were observed in response to oxybutynin (1 µM), solifenacin (1 µM), tolterodine (1 µM), darifenacin (100 nM), trospium (100 nM) and fesoterodine (100 nM). This shift was consistent in U&LP samples, with no significant differences between the two layers.ConclusionsThe data suggests that clinical antimuscarinics are as effective at inhibiting tonic contractions of the U&LP as they are on detrusor, presenting the U&LP as an alternate target of these medications in the treatment of lower urinary tract symptoms.