Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle

C. R. Chapple*, S. C. Radley, S. W. Martin, D. J. Sellers, R. Chess-Williams

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)

Abstract

OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 μmol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pK B values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT 4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

Original languageEnglish
Pages (from-to)599-604
Number of pages6
JournalBJU International
Volume93
Issue number4
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

Fingerprint

Overactive Urinary Bladder
Cholinergic Agents
Electric Stimulation
Serotonin
Muscles
Serotonin 5-HT4 Receptor Antagonists
Receptors, Serotonin, 5-HT4
Cisapride
Neurogenic Urinary Bladder
Serotonin Receptors
Serotonin 5-HT4 Receptor Agonists
Methiothepin
Receptors, Serotonin, 5-HT3
Ondansetron
Ketanserin
Serotonin Antagonists

Cite this

@article{55014237509a49e3a03ccd1f5eed291d,
title = "Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle",
abstract = "OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 μmol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pK B values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT 4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.",
author = "Chapple, {C. R.} and Radley, {S. C.} and Martin, {S. W.} and Sellers, {D. J.} and R. Chess-Williams",
year = "2004",
month = "3",
doi = "10.1111/j.1464-410X.2003.04681.x",
language = "English",
volume = "93",
pages = "599--604",
journal = "British Journal of Urology",
issn = "1464-410X",
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Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle. / Chapple, C. R.; Radley, S. C.; Martin, S. W.; Sellers, D. J.; Chess-Williams, R.

In: BJU International, Vol. 93, No. 4, 03.2004, p. 599-604.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle

AU - Chapple, C. R.

AU - Radley, S. C.

AU - Martin, S. W.

AU - Sellers, D. J.

AU - Chess-Williams, R.

PY - 2004/3

Y1 - 2004/3

N2 - OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 μmol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pK B values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT 4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

AB - OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 μmol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pK B values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT 4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

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DO - 10.1111/j.1464-410X.2003.04681.x

M3 - Article

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EP - 604

JO - British Journal of Urology

JF - British Journal of Urology

SN - 1464-410X

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