On the origin of spontaneous activity in the bladder

Abstract

ObjectivesTo characterise separately the pharmacological profiles of spontaneous contractions from the mucosa and detrusor layers of the bladder wall and to describe the relationship in mucosa between adenosine triphosphate (ATP) release and spontaneous contractions. Materials and MethodsSpontaneous contractions were measured (36°C) from isolated mucosa or detrusor preparations, and intact (mucosa + detrusor) preparations from guinea-pig bladders. Potential modulators were added to the superfusate. The percentage of smooth muscle was measured in haematoxylin and eosin stained sections. ATP release was measured in superfusate samples from a fixed point above the preparation using a luciferin-luciferase assay. ResultsThe magnitude of spontaneous contractions was in the order intact >mucosa >detrusor. The percentage of smooth muscle was least in mucosa and greatest in detrusor preparations. The pharmacological profiles of spontaneous contractions were different in mucosa and detrusor in response to P2X or P2Y receptor agonists, adenosine and capsaicin. The intact preparations showed responses intermediate to those from mucosa and detrusor preparations. Low extracellular pH generated large changes in detrusor, but not mucosa preparations. The mucosa preparations released ATP in a cyclical manner, followed by variations in spontaneous contractions. ATP release was greater in mucosa compared with detrusor, augmented by carbachol and reversed by the M 2 -selective antagonist, methoctramine. ConclusionsThe different pharmacological profiles of bladder mucosa and detrusor, implies different pathways for contractile activation. Also, the intermediate responses from intact preparations implies functional interaction. The temporal relationship between cyclical variation of ATP release and amplitude of spontaneous contractions is consistent with ATP release controlling spontaneous activity. Carbachol-mediated ATP release was independent of active contractile force.

Mucosal modulation of contractility in bladder strips from normal and overactive rat models and the effect of botulinum toxin A on overactive bladder strips

“…This phenomenon has also been reported for guinea‐pig bladder where removal of the mucosa resulted in reduced mucosa‐free strip spontaneous activity . There may be contractile elements within the mucosal layer which contribute to the larger activity in intact bladder strips; in guinea‐pig bladder, this has been attributed to muscularis mucosae smooth muscle contraction; however, this is perhaps unlikely to be the case in the present study given that such a tissue layer has not been reported for rat bladder . An explanation for enhanced activity in normal bladder intact strips may involve release of excitatory factors such as ATP from the mucosal layer which would act to enhance contraction of the detrusor smooth muscle …”

“…Experimentally, spontaneous contractions in ex vivo bladder strips from human or rodent bladders are regarded to be representative of non‐voiding contractions, which are pronounced in pathophysiologies. Intact strips exhibit robust spontaneous contractions; interestingly mucosal and detrusor layers separated by sharp dissection also have spontaneous contractions . Smooth muscle in the mucosa known as muscularis mucosae has physiological and pharmacological properties that are distinct from detrusor smooth muscle and have been reported for some species but not rat .…”

The Role of the Mucosa in Normal and Abnormal Bladder Function

“…Under resting conditions, mucosal ATP release is cyclical with a periodicity of about 10 min. and this is reflected in a similar periodicity of the integral of spontaneous contractility but with a delay of a few minutes . It might be suggested that ATP release form urothelium diffuses within the mucosa to modulate contractility activity.…”

The role of the mucosa in modulation of evoked responses in the spinal cord injured rat bladder

“…Interaction between the detrusor and mucosa is known to generate or augment spontaneous contractions, and is readily confirmed by the marked reduction in this activity in tissues in which the mucosa has been removed . This excitatory modulation of bladder function by the mucosa may serve to maintain adequate tone during physiologic bladder filling.…”