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.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:659554 |
| Date | January 2015 |
| Creators | Birch, Rebecca Elizabeth |
| Contributors | Wildman, Scott |
| Publisher | University of Kent |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | https://kar.kent.ac.uk/50031/ |
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