Consistencies between carbachol-induced contractions to clinical antimuscarinics in differently aged porcine bladders

Vineesha Veer, Russ Chess-Williams, Christian Moro*

*Corresponding author for this work

Research output: Contribution to conferenceAbstractResearchpeer-review

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Abstract

Introduction: The first-line pharmaceutical therapies for managing overactive bladder (OAB) are antimuscarinics (Moro et al., 2011) where they inhibit spontaneous contractions during the filling phase by blocking the actions of acetylcholine. While clinically used antimuscarinics can inhibit contractions in juvenile models (Veer et al., 2023), it is unclear if they were as effective in older tissue samples. As the prevalence of OAB increases with age, it is likely that there may be receptor or functional alterations within the urinary bladder that could impact tissue responses to this drug class.

Aims. This study aims to find the differences in the ability of commonly prescribed antimuscarinics to inhibit contractions of the detrusor and compare these responses in juvenile and adult porcine tissues.

Methods: Strips of porcine detrusor from the adult or juvenile model were mounted in carbogen-gassed Krebs-bicarbonate solution at 37°C. The tissues were paired with carbachol concentration-response curves performed in the absence or presence of oxybutynin (1µM), solifenacin (1µM) darifenacin (100nM), tolterodine (1µM), trospium (100nM) and fesoterodine (100nM). Concentrations were chosen to ensure complete concentration-response curves in response to carbachol. pEC50 values for each curve were analysed and estimated affinities calculated. Ethical approval was not required for this study as tissues were sourced from the local abattoir after slaughter for the routine commercial provision of food.

Results: A right parallel shift was produced from the control in the juvenile detrusor for all antimuscarinics, with estimated affinities calculated for oxybutynin (7.47, n = 10) solifenacin (6.73, n = 8), darifenacin (7.58, n = 11), tolterodine (8.09, n = 8), trospium (8.69, n = 8) and fesoterodine (8.67, n = 8). A right parallel shift was produced from the control in the adult detrusor for all antimuscarinics, with estimated affinities calculated for oxybutynin (7.44, n = 9) solifenacin (6.63, n = 8), darifenacin (7.95, n = 9), tolterodine (7.93, n = 8), trospium (9.30, n = 9) and fesoterodine (8.54, n = 8). Comparisons of estimated affinities for each antimuscarinic between juvenile and adult tissues revealed no differences in each tissue's functional response to the six antimuscarinics (p > 0.05).

Discussion: Although preliminary, with this study ongoing, there appears to be no significant differences between detrusor functional responses to antimuscarinics of differently aged porcine samples. Further supporting that these medications can assist in the treatment of OAB and lower urinary tract symptoms in the detrusor layer. Differences in compliance may be due to lifestyle or behavioural changes with age rather than alterations in the tissues ability to respond to the prescribed medication themselves.
Original languageEnglish
PagesP645
Number of pages1
Publication statusPublished - 24 Nov 2023
EventASCEPT Annual Scientific Meeting 2023: Transformational Pharmacology & Toxicology - International Convention Centre, Sydney, Australia
Duration: 20 Nov 202323 Nov 2023
https://www.asceptasm.com/2023-annual-scientific-meeting/program-and-speakers/

Conference

ConferenceASCEPT Annual Scientific Meeting 2023
Country/TerritoryAustralia
CitySydney
Period20/11/2323/11/23
Internet address

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