Thesis Abstract and Dissertation Abstracts
The influence of Prostaglandin E2 on bradykinin induced depolarization, generation and conduction of action potentials in the isolated vagus nerve
Abstract Category: Science
Course / Degree: MSc Pharmacology
Institution / University: Kings College London, University of London , United Kingdom
Published in: 2005
In this study we have investigated the sensitising effect that PGE2 has on the action of bradykinin (BK) in both depolarising the resting membrane potential and in action potential generation and propagation in the isolated, desheathed vagus nerve of the rat using an extra cellular grease gap recording technique. Treatment with proinflammatory PGE2 (1µM) produced a significant increase in the bradykinin (1µM) induced depolarisation of the vagus nerve but had no effect on the action potential generation and propagation. We hypothesise that this sensitisation is elicited by the vanilloid capsaicin sensitive receptor TRPV1. Activation of intracellular PKA using a membrane-permeant analogue of cyclic AMP i.e. dbcAMP (2mM) also increased the neuronal responses elicited by bradykinin (1µM) in a manner analogous to that produced by PGE2 (1µM). Treatment of the isolated vagus nerve with the phorbol ester PDBu (1µM) directly caused a depolarisation of the isolated vagus nerve as well as increasing the neuronal responses elicited by bradykinin (1µM) in a similar manner to that produced by PGE2 (1µM). Inclusion of a non-specific protein kinase inhibitor staurosporin (1µM) completely suppressed the sensitisation produced by PGE2 (1µM) or PDBu (1µM) but had no effect on the response produced by capsaicin (1µM). The application of the capsaicin antagonist ruthenium red (1µM) completely abolished the sensitisation produced by PGE2 (1µM) PDBu (1µM) and capsaicin (1µM). Taken together, these observations suggest that the PGE2 sensitisation of the BK induced depolarisation is mimicked by both activation of the PKA and PKC signalling pathways by a process that is completely blocked by the TRPV1 antagonist ruthenium red and staurosporin. Suggesting a pivotal role for the TRPV1 channel in the PGE2 and BK induced response.
Thesis Keywords/Search Tags:
Rat vagus nerve; prostaglandin E 2;BK; depolarisation; action potential; excitability; PKA; PKC; TRPV1 receptor
This Thesis Abstract may be cited as follows:
MUGERA C.M. & DOCHERTY R.J. (2005)
Submission Details: Thesis Abstract submitted by Charles Mugera from United States on 24-Aug-2010 19:18.
Abstract has been viewed 2561 times (since 7 Mar 2010).
Charles Mugera Contact Details: Email: mutithi@yahoo.com Phone: 4102277261
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