Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples

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Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples. / Mader, Robert; Kocher, Thomas; Haier, Joerg; Wieczorek, Grazyna; Pfannkuche, Hans-Juergen; Ito, Moriko.

in: EUR J GASTROEN HEPAT, Jahrgang 18, Nr. 9, 09.2006, S. 945-50.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{97e594da106f470f94e263bc39b402c0,
title = "Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples",
abstract = "BACKGROUND: The serotonin type 4 (5-HT4) receptor has been associated with functions of the gastrointestinal tract such as modulation of the peristaltic reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been shown to accelerate gastric emptying and improve symptoms of constipation in animals and humans. However, detailed data on the expression profile and on the localization of this receptor subtype are lacking so far.OBJECTIVE: To study the pattern and expression levels of 5-HT4 receptor messenger RNA expression in the gut.METHOD: Normal tissue samples were collected from the whole gastrointestinal tract of patients undergoing abdominal surgery and, in addition, of monkeys. We performed a comprehensive analysis of 5-HT4 receptor expression by quantitative reverse transcription-polymerase chain reaction, using human and non-human primate tissues from the oesophagus to the rectum. In addition, the brain and heart of non-human primates were analysed.RESULTS: Significantly higher levels of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum, ileum and caecum and also in the corresponding non-human primate gut segments, ranging from 2- to 12-fold compared with the liver. No differences were found between females and males of both human and non-human primates.CONCLUSIONS: These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.",
keywords = "Animals, Female, Gastrointestinal Tract, Humans, Male, Primates, RNA, Messenger, Receptors, Serotonin, 5-HT4, Reverse Transcriptase Polymerase Chain Reaction, Sex Factors",
author = "Robert Mader and Thomas Kocher and Joerg Haier and Grazyna Wieczorek and Hans-Juergen Pfannkuche and Moriko Ito",
year = "2006",
month = sep,
doi = "10.1097/01.meg.0000228975.87645.27",
language = "English",
volume = "18",
pages = "945--50",
journal = "EUR J GASTROEN HEPAT",
issn = "0954-691X",
publisher = "Lippincott Williams and Wilkins",
number = "9",

}

RIS

TY - JOUR

T1 - Investigation of serotonin type 4 receptor expression in human and non-human primate gastrointestinal samples

AU - Mader, Robert

AU - Kocher, Thomas

AU - Haier, Joerg

AU - Wieczorek, Grazyna

AU - Pfannkuche, Hans-Juergen

AU - Ito, Moriko

PY - 2006/9

Y1 - 2006/9

N2 - BACKGROUND: The serotonin type 4 (5-HT4) receptor has been associated with functions of the gastrointestinal tract such as modulation of the peristaltic reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been shown to accelerate gastric emptying and improve symptoms of constipation in animals and humans. However, detailed data on the expression profile and on the localization of this receptor subtype are lacking so far.OBJECTIVE: To study the pattern and expression levels of 5-HT4 receptor messenger RNA expression in the gut.METHOD: Normal tissue samples were collected from the whole gastrointestinal tract of patients undergoing abdominal surgery and, in addition, of monkeys. We performed a comprehensive analysis of 5-HT4 receptor expression by quantitative reverse transcription-polymerase chain reaction, using human and non-human primate tissues from the oesophagus to the rectum. In addition, the brain and heart of non-human primates were analysed.RESULTS: Significantly higher levels of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum, ileum and caecum and also in the corresponding non-human primate gut segments, ranging from 2- to 12-fold compared with the liver. No differences were found between females and males of both human and non-human primates.CONCLUSIONS: These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.

AB - BACKGROUND: The serotonin type 4 (5-HT4) receptor has been associated with functions of the gastrointestinal tract such as modulation of the peristaltic reflex, smooth muscle tone, intestinal secretion and visceral sensitivity. The activation of peripheral 5-HT4 receptors with agonists such as tegaserod has been shown to accelerate gastric emptying and improve symptoms of constipation in animals and humans. However, detailed data on the expression profile and on the localization of this receptor subtype are lacking so far.OBJECTIVE: To study the pattern and expression levels of 5-HT4 receptor messenger RNA expression in the gut.METHOD: Normal tissue samples were collected from the whole gastrointestinal tract of patients undergoing abdominal surgery and, in addition, of monkeys. We performed a comprehensive analysis of 5-HT4 receptor expression by quantitative reverse transcription-polymerase chain reaction, using human and non-human primate tissues from the oesophagus to the rectum. In addition, the brain and heart of non-human primates were analysed.RESULTS: Significantly higher levels of 5-HT4 receptor mRNA were measured in the human stomach, duodenum, jejunum, ileum and caecum and also in the corresponding non-human primate gut segments, ranging from 2- to 12-fold compared with the liver. No differences were found between females and males of both human and non-human primates.CONCLUSIONS: These results show 5-HT4 receptor mRNA expression throughout the gastrointestinal tract in humans and primates, and also support the preclinical and clinical findings of 5-HT4 receptors ligands exhibiting multiple effects throughout the gastrointestinal tract.

KW - Animals

KW - Female

KW - Gastrointestinal Tract

KW - Humans

KW - Male

KW - Primates

KW - RNA, Messenger

KW - Receptors, Serotonin, 5-HT4

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Sex Factors

U2 - 10.1097/01.meg.0000228975.87645.27

DO - 10.1097/01.meg.0000228975.87645.27

M3 - SCORING: Journal article

C2 - 16894306

VL - 18

SP - 945

EP - 950

JO - EUR J GASTROEN HEPAT

JF - EUR J GASTROEN HEPAT

SN - 0954-691X

IS - 9

ER -