Introduction: Underactive bladder is a complex clinical condition with a limited amount of research focused on identifying the mechanisms underlying its presentation. Most commonly, patients present with urgency, weak stream, nocturia, and urinary frequency. Underactive bladder is a multifactorial condition that can result from a variety of pathological processes, including idiopathic, neurogenic, myogenic or functional. However, there is limited research into the mechanisms underlying this disorder. Aim: This study aimed to identify potential receptors which could mediate contractions of the urinary bladder urothelium (1-3). Methods: Porcine urothelial strips were mounted in gassed Krebs-bicarbonate solution at 37°C and the tissue baseline tension (grams) was recorded before and after the addition of agonists as per prior research (4, 5). Ethical approval was not required as tissues were sourced from the local abattoir after slaughter for the routine commercial provision of food. Data obtained was analysed using paired Students t-tests. Results: The urothelium exhibited strong contractions upon receptor stimulation, with particularly rapid responses to many of the G protein-coupled receptor agonists. Contractions were induced by (mean ± SEM): carbachol 4.06 ± 0.43g (1µM, P<0.001, n=11); histamine 1.41 ± 0.29g (100µM, P<0.01, n=7); 5-HT 4.38 ± 0.53g (100µM, P<0.001, n=8); α,β-methylene ATP 1.88 ± 0.27 (10µM, P<0.001, n=8); and neurokinin-A 2.3 ± 0.25g (300nM, P<0.001, n=8). Conclusions: The strongest contractions were induced by stimulation of the muscarinic and 5-HT receptors, with plans for follow-up experimets to identify the influence of calcium and second-messenger mechanisms involved. A greater understanding into the various mediators of contraction may help identify future therapeutic targets to be employed in the pharmaceutical management of underactive bladder. In addition, further categorising the contractile responses of these receptors will provide further insights into the methods of contraction within the urinary bladder wall.
Physiology 2021 (2021) Proc Physiol Soc 48, OC35
Oral Communications: Potential targets for underactive bladder treatments: Receptor-mediated contractions of the urinary bladder urothelium
Charlotte Phelps1, Russ Chess-Williams1, Christian Moro1
1 Bond University, Gold Coast, Australia
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Where applicable, experiments conform with Society ethical requirements.