Mechanisms controlling ureteral motility

Student thesis: Doctoral Thesis


Medical expulsive therapy can be administered to treat ureteral calculi by relieving ureteral colic and increasing stone passage rate. It is vital to have a greater understanding of the mechanisms controlling ureteral contraction, as this may reveal novel mechanisms and identify targets for the development of more effective pharmacological agents for medical expulsive therapy. The overall aim of this thesis was to elucidate the mechanisms controlling contractility of the ureter. Functional organ bath studies with isolated porcine ureteral tissues were used to examine key systems involved in ureteral smooth muscle contraction. The findings demonstrate that G-protein coupled receptor-mediated contractile responses of ureteral tissues in response to muscarinic receptor, α1adrenoceptor and 5-HT receptor stimulation differ with age and the latter two appear to play more dominant roles in mediation of ureteral smooth muscle contraction. Muscarinic and α1-adrenoceptor-stimulated responses are increased in tissues from older animals compared to younger animals and vice versa in 5-HT-stimulated contractions. The 5-HT2A receptor subtype appears to be responsible for 5-HT-mediated contractile responses, although, this might be more complex with age. While it was clear that this is the sole functional receptor subtype in ureteral tissues from the younger animals, the findings suggested that this might not be the case in ureteral tissues from older animals. In the study of intracellular signalling pathways, it was observed that the Rho-kinase pathway plays a vital role in mediation of contractile responses in the ureter. Additionally, the inhibitory effect of urothelium and specifically, urothelium-derived inhibitory factor on contractile responses was evident in the isolated ureter and adenosine triphosphate was identified as a likely candidate for this inhibitory mediator. Conclusively, age-related changes are apparent in every mechanism that was investigated, indicating that ageing might an important factor to be considered in management of ureteral colic.
Date of Award11 Feb 2017
Original languageEnglish
SupervisorDonna Sellers (Supervisor) & Russ Chess-Williams (Supervisor)

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