Davis, Clare Louie;
(2001)
The expression and regulation of kinin receptors in rat bladder smooth muscle cells.
Doctoral thesis (University College London), University College London.
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Abstract
Kinins are important inflammatory mediators that have potent effects on a variety of cell types via B1 and B2 receptors. This thesis aimed to examine kinin receptor expression and regulation in rat bladder smooth muscle cells. The pharmacological profile of the responses of these cells to B1 and B2 agonists in a functional assay, measuring 45Ca efflux, in conjunction with radioligand binding experiments, was consistent with the cells expressing both B1 and B2 receptors. In addition, the rat specific kinin, T-kinin, and its putative breakdown product, des-Arg11-T-kinin, were potent and selective B2 and B1 agonists respectively, with selectivity for rat over human kinin receptors. The pro-inflammatory cytokine IL-I upregulated the responsiveness of the rat bladder cells to B1 agonists, but had no effect on responses to B2 agonists. The effect of IL-1 was inhibited by agents that inhibit protein synthesis such as cycloheximide and dexamethasone. This reflected increased expression of the B1 receptor as IL-1 increased B1 receptor mRNA and specific binding of [3H]- des-Arg10-kallidin. A novel mechanism by which B1 responses can be modulated was elucidated. Treatment with dibutyryl cAMP also lead to an increase in B1 receptor-evoked 45Ca efflux with no effect on B2 receptor-mediated responses. Although the increased responsiveness induced by dibutyryl cAMP was inhibited by cycloheximide and dexamethasone, there was no increase in B1 receptor mRNA or in [3H]-des-Arg10-kallidin binding. This suggests that dibutyryl cAMP stimulates the expression of a factor that acts downstream of the B1 receptor to increase agonist-evoked 45Ca efflux. The results suggest that, during inflammation, the expression and function of B1 receptors in the bladder may be increased by pro-inflammatory cytokines, whilst agents that elevate cAMP may increase B1 receptor-mediated responses. In contrast B2 mediated responses do not appear to be upregulated by inflammatory mediators in bladder smooth muscle cells.
Type: | Thesis (Doctoral) |
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Qualification: | University College London |
Title: | The expression and regulation of kinin receptors in rat bladder smooth muscle cells. |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis Digitised by Proquest. |
URI: | https://discovery.ucl.ac.uk/id/eprint/10121309 |
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