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Title: Bradykinin induced contraction of human gallbladder muscle in vitro
Author: Brennan, Hugh
ISNI:       0000 0001 3478 6521
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2004
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The initial work for this thesis looked at the effects of bradykinin on human gallbladder contractility. The aim was to determine if BK had an effect on human gallbladder tissue and if so, what BK receptors were involved and to investigate if other mechanisms had an influence on this effect. Contractility tests were used to examine the BK receptor types, selective antagonists of BK1 and BK2 were used. Stone bearing gallbladders were obtained from patients undergoing cholecystectomy for gallbladder disease and healthy gallbladders were removed from patients undergoing resections for pancreatic or hepatic malignancy. Only macroscopically normal tissue was used. A full thickness segment from the anterior aspect of the body of the gallbladder was removed and placed in cold Krebs solution. Muscle strips were cut from the segment and suspended in Krebs solution in an organ bath at 37°C, gassed with 5% CO₂ in oxygen. The strips were connected to an isotonic transducer under a 1g pre-load. After 2 hours equilibration, a concentration-response curve to BK was obtained (0.1μM-100μM), and washed out until a stable baseline had returned. It was determined that BK contracted human gallbladder smooth muscle in vitro and that both BK1 and BK2 receptors were involved in this response. It was argued that a difference in receptor population exists between normal and stone-bearing tissue. It was also suggested that another class of BK receptor maybe present. There is also evidence to suggest that a third BK receptor or another independent mechanism may mediate this response. Having established the initial results, the interaction of the BK response with various other substances, mediators and mechanisms known to have an effect on gallbladder motility had to be explored. BK appears to have a direct effect on human gallbladder smooth muscle. The BK-mediated concentration of human gallbladder depends on the release of intracellular calcium sources.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available