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The effect of serine proteases on ATP-signalling in renal tubules and medullary micro vessels

Birch, Rebecca Elizabeth (2015) The effect of serine proteases on ATP-signalling in renal tubules and medullary micro vessels. Doctor of Philosophy (PhD) thesis, University of Kent. (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

An estimated 2% of the human genome encodes for proteolytic enzymes. It is becoming increasingly apparent that serine proteases have diverse and critical roles in many physiological and pathophysiological processes. Studies investigating the role of serine proteases in the kidney have focussed primarily on their pro-inflammatory effects and their ability to cleave and activate the epithelial sodium channel (ENaC). P2X receptors, which are structurally very similar to ENaC and have been identified throughout the nephron and in the renal vasculature, are thought to contribute to the regulation of tubular transport mechanism and renal haemodynamics, as well as be involved in several renal pathologies. It is shown here that the serine protease, trypsin, has a significant inhibitory effect on recombinant human P2X3 and P2X7 receptor activity. Moreover, it is shown that trypsin may also have an inhibitory effect on purinergic signalling in the mouse cortical collecting duct. In addition, the single channel activity of P2X receptors expressed on the apical membrane of renal collecting duct epithelial cells is described for the first time. Finally, a novel use of the live-tissue slice method is described and the first direct evidence showing trypsin causes significant morphological changes in renal tubules and medullary microvessels in situ is provided. Collectively, data presented here provides evidence to suggest that serine proteases may contribute to several aspects of renal function that have not previously been explored.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Wildman, Scott S.P.
Thesis advisor: Peppiatt-Wildman, Claire M.
Thesis advisor: Unwin, Robert J
Uncontrolled keywords: Proteases, purinergic signalling, renal
Subjects: R Medicine > RS Pharmacy and materia medica
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Users 1 not found.
Date Deposited: 05 Aug 2015 15:00 UTC
Last Modified: 29 May 2019 15:53 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/50031 (The current URI for this page, for reference purposes)
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