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

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

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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",
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language = "English",
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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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