5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria

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Abstract

OBJECTIVES: To examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments.

METHODS: Strips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, Nω-nitro-l-arginine and indomethacin. Responses to α-methyl-5-HT were also examined.

RESULTS: Strips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 ± 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of Nω-nitro-l-arginine (100 μmol/L) or indomethacin (5 μmol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2 , 100 nmol/L), RS102221 (5-HT2C , 30 nmol/L), ondansetron (5-HT3 , 30 nmol/L), GR113808, (5-HT4 , 100 nmol/L), SB699551 (5-HT5 , 10 nmol/L), SB399885 (5-HT6 , 100 nmol/L) and SB269970 (5-HT7 , 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 μmol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9.

CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.

Original languageEnglish
Pages (from-to)946-951
Number of pages6
JournalInternational Journal of Urology
Volume23
Issue number11
DOIs
Publication statusPublished - Nov 2016

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Receptor, Serotonin, 5-HT2A
Urothelium
Serotonin
Mucous Membrane
Swine
Indomethacin
Arginine
Methiothepin
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT2 Receptor Antagonists
Ondansetron
Ketanserin
Serotonin Antagonists
Bicarbonates
Urinary Bladder

Cite this

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title = "5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria",
abstract = "OBJECTIVES: To examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments.METHODS: Strips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, Nω-nitro-l-arginine and indomethacin. Responses to α-methyl-5-HT were also examined.RESULTS: Strips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 ± 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of Nω-nitro-l-arginine (100 μmol/L) or indomethacin (5 μmol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2 , 100 nmol/L), RS102221 (5-HT2C , 30 nmol/L), ondansetron (5-HT3 , 30 nmol/L), GR113808, (5-HT4 , 100 nmol/L), SB699551 (5-HT5 , 10 nmol/L), SB399885 (5-HT6 , 100 nmol/L) and SB269970 (5-HT7 , 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 μmol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9.CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.",
author = "Christian Moro and Lily Edwards and Russ Chess-Williams",
note = "{\circledC} 2016 The Japanese Urological Association.",
year = "2016",
month = "11",
doi = "10.1111/iju.13172",
language = "English",
volume = "23",
pages = "946--951",
journal = "International Journal of Urology",
issn = "0919-8172",
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}

5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria. / Moro, Christian; Edwards, Lily; Chess-Williams, Russ.

In: International Journal of Urology, Vol. 23, No. 11, 11.2016, p. 946-951.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 5-HT2A receptor enhancement of contractile activity of the porcine urothelium and lamina propria

AU - Moro, Christian

AU - Edwards, Lily

AU - Chess-Williams, Russ

N1 - © 2016 The Japanese Urological Association.

PY - 2016/11

Y1 - 2016/11

N2 - OBJECTIVES: To examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments.METHODS: Strips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, Nω-nitro-l-arginine and indomethacin. Responses to α-methyl-5-HT were also examined.RESULTS: Strips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 ± 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of Nω-nitro-l-arginine (100 μmol/L) or indomethacin (5 μmol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2 , 100 nmol/L), RS102221 (5-HT2C , 30 nmol/L), ondansetron (5-HT3 , 30 nmol/L), GR113808, (5-HT4 , 100 nmol/L), SB699551 (5-HT5 , 10 nmol/L), SB399885 (5-HT6 , 100 nmol/L) and SB269970 (5-HT7 , 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 μmol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9.CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.

AB - OBJECTIVES: To examine the effect of 5-hydroxytryptamine (5-HT; serotonin) on the contractile properties of the urothelium and lamina propria, as a better understanding of bladder physiology might aid the development of new treatments.METHODS: Strips of porcine urothelium and lamina propria were suspended in gassed Krebs-bicarbonate solution, and cumulative concentration-response curves for 5-HT were generated in the absence and presence of 5-HT antagonists, Nω-nitro-l-arginine and indomethacin. Responses to α-methyl-5-HT were also examined.RESULTS: Strips of urothelium/lamina propria developed spontaneous contractions, whereas the addition of 5-HT induced concentration-dependent increases in contractile tone with maximal contractions of 50.43 ± 2.78 mN/g tissue weight (n = 100). Tonic contractions to 5-HT were unchanged in the presence of Nω-nitro-l-arginine (100 μmol/L) or indomethacin (5 μmol/L). Selective concentrations of the antagonists methiothepin (5-HT1&2 , 100 nmol/L), RS102221 (5-HT2C , 30 nmol/L), ondansetron (5-HT3 , 30 nmol/L), GR113808, (5-HT4 , 100 nmol/L), SB699551 (5-HT5 , 10 nmol/L), SB399885 (5-HT6 , 100 nmol/L) and SB269970 (5-HT7 , 10 nmol/L) did not influence responses to 5-HT. However, the 5-HT2A antagonist, ketanserin (30-300 μmol/L), caused a shift of the 5-HT curve yielding an affinity estimate of 7.9.CONCLUSIONS: The results show that contractile responses of the urothelium/lamina propria to 5-HT are predominantly mediated through the 5-HT2A receptor.

U2 - 10.1111/iju.13172

DO - 10.1111/iju.13172

M3 - Article

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EP - 951

JO - International Journal of Urology

JF - International Journal of Urology

SN - 0919-8172

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