Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice

Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in pri...

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Veröffentlicht in:Laboratory investigation 2012-05, Vol.92 (5), p.769-782
Hauptverfasser: Matsumoto, Kenjiro, Lo, Mee Wah, Hosoya, Takuji, Tashima, Kimihito, Takayama, Hiromitsu, Murayama, Toshihiko, Horie, Syunji
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container_end_page 782
container_issue 5
container_start_page 769
container_title Laboratory investigation
container_volume 92
creator Matsumoto, Kenjiro
Lo, Mee Wah
Hosoya, Takuji
Tashima, Kimihito
Takayama, Hiromitsu
Murayama, Toshihiko
Horie, Syunji
description Abnormalities of primary afferent nerve fibers are strongly associated with the visceral hypersensitivity state in inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice.
doi_str_mv 10.1038/labinvest.2012.14
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Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). 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Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Hyperalgesia - metabolism</topic><topic>Hyperalgesia - physiopathology</topic><topic>inflammatory bowel disease</topic><topic>Inflammatory Bowel Diseases - chemically induced</topic><topic>Inflammatory Bowel Diseases - metabolism</topic><topic>Inflammatory Bowel Diseases - physiopathology</topic><topic>Intestinal Mucosa - innervation</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Confocal</topic><topic>Nociception - drug effects</topic><topic>Other diseases. 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Hypersensitivity of afferent fibers occurs during inflammation. Therefore, to gain an insight into the alterations to receptors and channels expressed in primary afferent neurons, the current study aimed to investigate the time-dependent dynamic changes in levels of 5-hydroxytryptamine (5-HT)3 receptors, 5-HT4 receptors, transient receptor potential vanilloid type 1 (TRPV1) channels, and 5-HT regulatory factors in dextran sulfate sodium (DSS)-induced colitis model mice. 5-HT signaling molecules were detected by indirect staining with specific antibodies. TRPV1-immunoreactivity was detected by staining with fluorescein-conjugated tyramide amplification. To assess nociception, visceromotor responses (VMRs) to colorectal distension were measured by electromyography of abdominal muscles. Immunohistochemical analysis and VMRs to colorectal distention were measured during induction of DSS colitis (days 4 and 7). Inflammation led to downregulation of serotonin transporter immunoreactivities with concomitant increases in 5-HT and tryptophan hydroxylase-1-positive cell numbers. TRPV1-expressing nerve fibers gradually increased during DSS treatment. Abundant nonneuronal TRPV1-immunopositive cell-like structures were observed on day 7 of DSS treatment but not on day 4. The number of 5-HT3 receptor-expressing nerve fibers in the mucosa was increased on day 7. On the other hand, the number of 5-HT4 receptor-expressing nerve fibers in the mucosa decreased on day 7. We made the novel observation of increased expression of neuronal/nonneuronal TRPV1 channels and 5-HT3 receptors, and decreased expression of 5-HT4 receptors in the mucosa in a DSS-induced colitis model. Visceral hyperalgesia was observed on day 7 but not on day 4. A TRPV1 antagonist and a 5-HT3 receptor antagonist attenuated the visceral hyperalgesia to the control level. The alterations of 5-HT signaling via 5-HT3 receptors and of TRPV1 channels in mucosa may contribute to the visceral hypersensitivity in colitis model mice.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>22330338</pmid><doi>10.1038/labinvest.2012.14</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/250/249/2510/9
692/420
692/699/1503/1581/257
Animals
Biological and medical sciences
Biotechnology
Carbolines - pharmacology
Dextran Sulfate - administration & dosage
Dextran Sulfate - adverse effects
Disease Models, Animal
Electromyography
enteric nervous system
Fundamental and applied biological sciences. Psychology
Gastroenterology. Liver. Pancreas. Abdomen
Hyperalgesia - metabolism
Hyperalgesia - physiopathology
inflammatory bowel disease
Inflammatory Bowel Diseases - chemically induced
Inflammatory Bowel Diseases - metabolism
Inflammatory Bowel Diseases - physiopathology
Intestinal Mucosa - innervation
Intestinal Mucosa - metabolism
Investigative techniques, diagnostic techniques (general aspects)
Laboratory Medicine
Male
Medical sciences
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Nociception - drug effects
Other diseases. Semiology
Pathology
Pyrazines - pharmacology
Pyridines - pharmacology
Receptors, Serotonin, 5-HT3 - metabolism
Receptors, Serotonin, 5-HT4 - metabolism
research-article
serotonin
Serotonin - metabolism
Serotonin Antagonists - pharmacology
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Time Factors
TRPV Cation Channels - analysis
TRPV Cation Channels - antagonists & inhibitors
TRPV Cation Channels - metabolism
TRPV1
Tryptophan Hydroxylase - metabolism
Visceral Afferents - metabolism
Visceral Afferents - physiopathology
visceral hypersensitivity
title Experimental colitis alters expression of 5-HT receptors and transient receptor potential vanilloid 1 leading to visceral hypersensitivity in mice
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