Stretch‐ and carbachol‐induced ATP release from bladder wall preparations of young and aged mice. Issue 6 (12th June 2020)

• Record Type: Journal Article
• Authors: Nishikawa, Nobuyuki; Chakrabarty, Basu; Kitney, Darryl; Jabr, Rita; Kanai, Anthony; Fry, Christopher
• Is Part Of: Neurourology and urodynamics. Volume 39:Issue 6(2020:Aug.)
• Page Start: 1644
• Page End: 1652
• Publication Date: 2020-06-12
• Subjects: aged mice -- ATP release -- contractility -- muscarinic agonists -- stretch; Urinary organs -- Periodicals; Urodynamics -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1002/nau.24426
• Languages: English
• ISSNs: 0733-2467

Abstract

Abstract: Aims: Bladder wall stretch increases tissue tension and releases adenosine 5'‐triphosphate (ATP) as part of a transduction process to sense bladder filling. Aging is associated with bladder fibrosis to produce a stiffer bladder wall: this may augment ATP release and contribute to age‐dependent urgency. Muscarinic agonists also release ATP and present a potential target for antimuscarinic agents, but its age‐dependency is unknown. This study aimed, in young and old mice, to: (a) quantify the relationship between bladder wall stiffness and stretch‐dependent ATP release and; (b) characterize muscarinic agonist‐dependent release. Methods: ATP release from young (9‐12 weeks) and aged (24 months) mouse bladder wall was measured in vitro, with a luciferin‐luciferase assay, after stretch or carbachol exposure. Bladder wall stiffness, measured simultaneously during stretch, was compared to histological proportions of connective tissue and detrusor muscle. Results: With young mice, stretch‐activated ATP release required an intact mucosa and was positively associated with wall stiffness. ATP release by carbachol was about four‐fold greater compared to stretch. With aged mice: ATP release varied a hundred‐fold and no association with stiffness; carbachol release diminished; connective tissue and mucosa thickness increased. Conclusions: With young mice, stretch, or muscarinic agonists potently induce bladder wall ATP release. Stretch‐dependent release is proportional to bladder wall stiffness, independent of the extent of stretch. With aged mice dependence of stretch‐activated ATP release with stiffness was lost. The huge variability of release suggests that aged mice do not form a homogenous cohort and may underlie the heterogeneity in bladder filling sensations.