A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity

Elizabeth J Edwards, Russ Chess-Williams, Christian Moro

Research output: Contribution to conferenceAbstractResearchpeer-review

Abstract

Introduction/Aim: Bladder dysfunction can lead to a range of debilitating conditions, and treatments are often associated with several side effects that substantially reduce quality of life. Research into alternative targets acting on bladder layers, including 5-hydroxytryptamine (5-HT, also termed serotonin) is extremely valuable. The aim of this study was to determine the effects of 5-HT on the contractile activity of the urothelium and lamina propria, and the likely mediating receptor.
Methods: Strips of porcine urothelium and lamina propria were suspended in 10mL organ baths filled with warm Krebs-bicarbonate solution. Cumulative dose-response curves using 5-Hydroxytryptamine were generated in the presence of the 5-HT antagonists, methiothepin, ketanserin, ondansetron and GR113808. Maximal tissue contractions were determined with carbachol doses. Data was analysed using a paired Student’s t-test.
Results: 5-HT application produced concentration-dependent contractions in the tissue. Maximal contractions to 5-HT (0.94±0.08g) were approximately 17% of carbachol-mediated contractions (n=37, 30µM). 5-HT stimulated contractions were unchanged in the presence of the nitric oxide synthesis inhibitor L-NNA (n=5, 100µM) or cyclooxygenase inhibitor indomethacin (n=4, 100µM). In the presence of the 5-HT1 antagonist responses were significantly (p?0.001) decreased (n=8, 10nM). Ketanserin (n=9, 30nM), ondansetron (n=13, 30nM) and GR113808 (n=8, 100nM) produced no significant changes in the 5-HT contractile response (all p=NSD).
Original languageEnglish
Publication statusPublished - 2015
EventThe Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference - Gold Coast, Australia
Duration: 3 Dec 20164 Dec 2016

Conference

ConferenceThe Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference
CountryAustralia
CityGold Coast
Period3/12/164/12/16

Fingerprint

Serotonin
Mucous Membrane
Urinary Bladder
Ondansetron
Urothelium
Ketanserin
Therapeutics
Carbachol
Methiothepin
Serotonin 5-HT1 Receptor Antagonists
Serotonin Antagonists
Cyclooxygenase Inhibitors
Bicarbonates
Baths
Indomethacin
Nitric Oxide
Swine
Quality of Life
Students
Research

Cite this

Edwards, E. J., Chess-Williams, R., & Moro, C. (2015). A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity. Abstract from The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference , Gold Coast, Australia.
Edwards, Elizabeth J ; Chess-Williams, Russ ; Moro, Christian. / A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity. Abstract from The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference , Gold Coast, Australia.
@conference{0796798bf4724c3e921fdcdef538b2c7,
title = "A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity",
abstract = "Introduction/Aim: Bladder dysfunction can lead to a range of debilitating conditions, and treatments are often associated with several side effects that substantially reduce quality of life. Research into alternative targets acting on bladder layers, including 5-hydroxytryptamine (5-HT, also termed serotonin) is extremely valuable. The aim of this study was to determine the effects of 5-HT on the contractile activity of the urothelium and lamina propria, and the likely mediating receptor.Methods: Strips of porcine urothelium and lamina propria were suspended in 10mL organ baths filled with warm Krebs-bicarbonate solution. Cumulative dose-response curves using 5-Hydroxytryptamine were generated in the presence of the 5-HT antagonists, methiothepin, ketanserin, ondansetron and GR113808. Maximal tissue contractions were determined with carbachol doses. Data was analysed using a paired Student’s t-test. Results: 5-HT application produced concentration-dependent contractions in the tissue. Maximal contractions to 5-HT (0.94±0.08g) were approximately 17{\%} of carbachol-mediated contractions (n=37, 30µM). 5-HT stimulated contractions were unchanged in the presence of the nitric oxide synthesis inhibitor L-NNA (n=5, 100µM) or cyclooxygenase inhibitor indomethacin (n=4, 100µM). In the presence of the 5-HT1 antagonist responses were significantly (p?0.001) decreased (n=8, 10nM). Ketanserin (n=9, 30nM), ondansetron (n=13, 30nM) and GR113808 (n=8, 100nM) produced no significant changes in the 5-HT contractile response (all p=NSD).",
author = "Edwards, {Elizabeth J} and Russ Chess-Williams and Christian Moro",
year = "2015",
language = "English",
note = "The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference ; Conference date: 03-12-2016 Through 04-12-2016",

}

Edwards, EJ, Chess-Williams, R & Moro, C 2015, 'A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity' The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference , Gold Coast, Australia, 3/12/16 - 4/12/16, .

A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity. / Edwards, Elizabeth J; Chess-Williams, Russ; Moro, Christian.

2015. Abstract from The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference , Gold Coast, Australia.

Research output: Contribution to conferenceAbstractResearchpeer-review

TY - CONF

T1 - A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity

AU - Edwards, Elizabeth J

AU - Chess-Williams, Russ

AU - Moro, Christian

PY - 2015

Y1 - 2015

N2 - Introduction/Aim: Bladder dysfunction can lead to a range of debilitating conditions, and treatments are often associated with several side effects that substantially reduce quality of life. Research into alternative targets acting on bladder layers, including 5-hydroxytryptamine (5-HT, also termed serotonin) is extremely valuable. The aim of this study was to determine the effects of 5-HT on the contractile activity of the urothelium and lamina propria, and the likely mediating receptor.Methods: Strips of porcine urothelium and lamina propria were suspended in 10mL organ baths filled with warm Krebs-bicarbonate solution. Cumulative dose-response curves using 5-Hydroxytryptamine were generated in the presence of the 5-HT antagonists, methiothepin, ketanserin, ondansetron and GR113808. Maximal tissue contractions were determined with carbachol doses. Data was analysed using a paired Student’s t-test. Results: 5-HT application produced concentration-dependent contractions in the tissue. Maximal contractions to 5-HT (0.94±0.08g) were approximately 17% of carbachol-mediated contractions (n=37, 30µM). 5-HT stimulated contractions were unchanged in the presence of the nitric oxide synthesis inhibitor L-NNA (n=5, 100µM) or cyclooxygenase inhibitor indomethacin (n=4, 100µM). In the presence of the 5-HT1 antagonist responses were significantly (p?0.001) decreased (n=8, 10nM). Ketanserin (n=9, 30nM), ondansetron (n=13, 30nM) and GR113808 (n=8, 100nM) produced no significant changes in the 5-HT contractile response (all p=NSD).

AB - Introduction/Aim: Bladder dysfunction can lead to a range of debilitating conditions, and treatments are often associated with several side effects that substantially reduce quality of life. Research into alternative targets acting on bladder layers, including 5-hydroxytryptamine (5-HT, also termed serotonin) is extremely valuable. The aim of this study was to determine the effects of 5-HT on the contractile activity of the urothelium and lamina propria, and the likely mediating receptor.Methods: Strips of porcine urothelium and lamina propria were suspended in 10mL organ baths filled with warm Krebs-bicarbonate solution. Cumulative dose-response curves using 5-Hydroxytryptamine were generated in the presence of the 5-HT antagonists, methiothepin, ketanserin, ondansetron and GR113808. Maximal tissue contractions were determined with carbachol doses. Data was analysed using a paired Student’s t-test. Results: 5-HT application produced concentration-dependent contractions in the tissue. Maximal contractions to 5-HT (0.94±0.08g) were approximately 17% of carbachol-mediated contractions (n=37, 30µM). 5-HT stimulated contractions were unchanged in the presence of the nitric oxide synthesis inhibitor L-NNA (n=5, 100µM) or cyclooxygenase inhibitor indomethacin (n=4, 100µM). In the presence of the 5-HT1 antagonist responses were significantly (p?0.001) decreased (n=8, 10nM). Ketanserin (n=9, 30nM), ondansetron (n=13, 30nM) and GR113808 (n=8, 100nM) produced no significant changes in the 5-HT contractile response (all p=NSD).

M3 - Abstract

ER -

Edwards EJ, Chess-Williams R, Moro C. A novel therapeutic bladder target? The influence of serotonin (5-HT) on urothelial and lamina propria contractile activity. 2015. Abstract from The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference The Gold Coast Health and Medical Research Conference , Gold Coast, Australia.