Hussain, Mahreen;
(2010)
The role of P1 receptors in regulating detrusor contraction: their relevance in the overactive bladder.
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
Bladder motor nerves co-release acetylcholine and ATP. ATP is degraded to adenosine at the neuro-muscular junction where it is hypothesized to modulate detrusor contraction by acting on Pl receptors. This thesis aimed to investigate the function, distribution and expression of Pl receptor subtypes in modulating guinea- pig and human detrusor contractility, and whether human bladder pathologies affected any actions. The contractile effects of adenosine and Pl-subtype (Ai, A2A, A2B, A3) selective agents were investigated using isolated detrusor strips, contracted by nerve-mediated field-stimulation or with agonists. Pl-receptor subtype expression in human detrusor samples, from both stable and overactive bladders, was determined; mRNA expression using the polymerase chain reaction and protein expression using Western blotting. Adenosine depressed both nerve- and agonist-mediated contractions. With human samples the effect was greater in overactive bladders compared to those from stable bladders; and more with neurogenic (NDO) compared to idiopathic (IDO) overactive bladders. ATP was preferentially released at lower stimulation frequencies, particularly from guinea-pig and overactive human samples. Adenosine depressed force more at low frequencies. The Ai-selective agent CPA had a major depressant effect in guinea-pig and NDO samples, less so in IDO and stable human samples, but less than with adenosine itself. With NDO samples A2B-receptor modulation also altered contraction; A2A and A3- receptor modulators had no significant effect. Ai-receptor expression and transcription was low in all sample groups. A2A-receptor expression was low in NDO samples, but A2B- and As-receptor expression and translation were equivalent in all groups. The data are consistent with the hypothesis that ATP is released from motor nerves, preferentially at low stimulation frequencies and that adenosine affects selectively ATP release. I hypothesise that pre-junctional Ai-receptors are the major Pl-receptor modulators, with a possible additional action of A2B-receptors in NDO bladders, along with possible non-selective effects of adenosine
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | The role of P1 receptors in regulating detrusor contraction: their relevance in the overactive bladder |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10209415 |
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