Future therapies for the treatment of bladder contractile disorders?

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Abstract

Strong and sustained bladder contractions are vital for voiding, however, if abnormal or spontaneous contractions occur during the filling stage, bladder dysfunction may arise. One common presentation is underactive bladder, where patients present with symptoms of urgency, weak stream, nocturia, and urinary frequency. However, there is a limited amount of research focussed on the mechanisms underlying underactive bladder, and therefore a paucity of treatment options available (1). This emphasises the need to identify novel targets in the urinary bladder that can be used in future therapies. This study aimed to determine the influence of extracellular calcium (Ca2+) in G protein-coupled receptor-mediated contraction of the urinary bladder urothelium and lamina propria (U&LP). Strips of U&LP were isolated from porcine bladder and suspended in organ baths containing Krebs solution at 37°C and perfused with carbogen gas. Tissue contractions were recorded before and after the addition of a single dose of GPCR agonist in the absence and presence of 1μM nifedipine or nominally zero Ca2+ solution. When receptor agonists carbachol (1μM), histamine (100μM), 5-HT (100μM), NKA (300nM), PGE2 (10μM), and ATII (100nM) were added to the tissues, U&LP baseline tension increased significantly for all activated receptors (p < 0.001). In the presence of the L-type Ca2+ channel inhibitor nifedipine (1μM), or nominally zero Ca2+ solution, receptor-mediated contractions were inhibited. On average, Ca2+ influx from extracellular sources was responsible for between 20–50% of receptor-mediated contractions. Extracellular Ca2+ plays an essential role across many physiological functions, and mediates not only contraction, but also key Ca2+-dependent systems which could be altered in bladder disorders. This study supports the suggestion of a prominent role of extracellular Ca2+ for urinary bladder contractile activity, presenting a mechanism potentially underlying underactive bladder.
Original languageEnglish
Pages3
Publication statusUnpublished - 14 Oct 2022
EventASCEPT Special Interest Group Virtual National Symposium: Advances in Urogenital and Gut Research Symposium - Virtual
Duration: 14 Oct 202214 Oct 2022

Conference

ConferenceASCEPT Special Interest Group Virtual National Symposium: Advances in Urogenital and Gut Research Symposium
Period14/10/2214/10/22

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