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  1. Article ; Online: Purinergic inhibitory regulation of esophageal smooth muscle is mediated by P2Y receptors and ATP-dependent potassium channels in rats.

    Shiina, Takahiko / Suzuki, Yuji / Horii, Kazuhiro / Sawamura, Tomoya / Yuki, Natsufu / Horii, Yuuki / Shimizu, Yasutake

    The journal of physiological sciences : JPS

    2024  Volume 74, Issue 1, Page(s) 26

    Abstract: Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an ... ...

    Abstract Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (K
    MeSH term(s) Animals ; Rats ; Muscle, Smooth/drug effects ; Muscle, Smooth/physiology ; Muscle, Smooth/metabolism ; Male ; Receptors, Purinergic P2Y/metabolism ; Esophagus/drug effects ; Esophagus/physiology ; Adenosine Triphosphate/metabolism ; Adenosine Triphosphate/pharmacology ; KATP Channels/metabolism ; Muscle Relaxation/drug effects ; Muscle Relaxation/physiology ; Rats, Wistar ; Muscle Contraction/drug effects ; Muscle Contraction/physiology ; Purinergic P2Y Receptor Antagonists/pharmacology ; Gastrointestinal Motility/drug effects ; Gastrointestinal Motility/physiology ; Rats, Sprague-Dawley
    Chemical Substances Receptors, Purinergic P2Y ; Adenosine Triphosphate (8L70Q75FXE) ; KATP Channels ; Purinergic P2Y Receptor Antagonists
    Language English
    Publishing date 2024-04-23
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 2234472-X
    ISSN 1880-6562 ; 1880-6546
    ISSN (online) 1880-6562
    ISSN 1880-6546
    DOI 10.1186/s12576-024-00916-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Sex differences in the central regulation of colorectal motility in response to noxious stimuli.

    Horii, Kazuhiro / Sawamura, Tomoya / Yuki, Natsufu / Shiina, Takahiko / Shimizu, Yasutake

    Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi

    2023  Volume 59, Page(s) 28–33

    Abstract: Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous ... ...

    Abstract Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous system. Noxious stimuli in the colorectum of anesthetized male rats enhance colorectal motility by activating monoaminergic neurons in descending pain inhibitory pathways from the brainstem to the lumbosacral spinal cord. These monoaminergic neurons release serotonin and dopamine into the lumbosacral spinal cord, resulting in the increment of colorectal motility. In female rats, in contrast, noxious stimuli in the colorectum have no effect on colorectal motility. We clarified that GABAergic inhibition in the lumbosacral spinal cord masks the enhancement of colorectal motility induced by monoamines in female animals. Considering that IBS patients often show visceral hypersensitivity and hyperalgesia, our studies suggest that differences in the descending neurons that respond to painful stimuli are involved in various sex differences in abnormal bowel habits.
    MeSH term(s) Female ; Rats ; Male ; Animals ; Irritable Bowel Syndrome ; Rats, Sprague-Dawley ; Sex Characteristics ; Spinal Cord/physiology ; Colorectal Neoplasms
    Language English
    Publishing date 2023-04-27
    Publishing country Japan
    Document type Journal Article
    ISSN 1884-8796
    ISSN (online) 1884-8796
    DOI 10.1540/jsmr.59.28
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Contribution of sex hormones to the sexually dimorphic response of colorectal motility to noxious stimuli in rats.

    Horii, Kazuhiro / Sawamura, Tomoya / Onishi, Ayaka / Yuki, Natsufu / Naitou, Kiyotada / Shiina, Takahiko / Shimizu, Yasutake

    American journal of physiology. Gastrointestinal and liver physiology

    2022  Volume 323, Issue 1, Page(s) G1–G8

    Abstract: Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this ...

    Abstract Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this study was to determine whether sex hormones are major contributing factors for sex-dependent differences in neural components of the spinal defecation center. Colorectal motility was measured using an in vivo method under ketamine and α-chloralose anesthesia in rats. Capsaicin was administered into the colorectal lumen as noxious stimuli. Orchiectomy in male rats had no effect on the capsaicin-induced response of colorectal motility. However, in ovariectomized female rats, capsaicin administration enhanced colorectal motility, though intact female animals did not show enhanced motility. When estradiol was administered by using a sustained-release preparation in ovariectomized female rats, capsaicin administration did not enhance colorectal motility unless a GABA
    MeSH term(s) Animals ; Capsaicin/pharmacology ; Colorectal Neoplasms ; Defecation/physiology ; Estradiol/pharmacology ; Female ; Gastrointestinal Motility/physiology ; Gonadal Steroid Hormones/pharmacology ; Male ; Rats ; Rats, Sprague-Dawley
    Chemical Substances Gonadal Steroid Hormones ; Estradiol (4TI98Z838E) ; Capsaicin (S07O44R1ZM)
    Language English
    Publishing date 2022-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00033.2022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Alterations in descending brain-spinal pathways regulating colorectal motility in a rat model of Parkinson's disease.

    Sawamura, Tomoya / Yuki, Natsufu / Aoki, Kanae / Horii, Kazuhiro / Horii, Yuuki / Naitou, Kiyotada / Tsukamoto, Shumpei / Shiina, Takahiko / Shimizu, Yasutake

    American journal of physiology. Gastrointestinal and liver physiology

    2023  Volume 326, Issue 2, Page(s) G195–G204

    Abstract: Patients with Parkinson's disease (PD) often have constipation. It is assumed that a disorder of the regulatory mechanism of colorectal motility by the central nervous system is involved in the constipation, but this remains unclear. The aim of this ... ...

    Abstract Patients with Parkinson's disease (PD) often have constipation. It is assumed that a disorder of the regulatory mechanism of colorectal motility by the central nervous system is involved in the constipation, but this remains unclear. The aim of this study was to investigate whether central neural pathways can modulate colorectal motility in a rat model of PD. PD model rats were generated by injection of 6-hydroxydopamine into a unilateral medial forebrain bundle and destruction of dopaminergic neurons in the substantia nigra. Colorectal motility was measured in vivo in anesthetized rats. Intraluminal administration of capsaicin, as a noxious stimulus, induced colorectal motility in sham-operated rats but not in PD rats. Intrathecally administered dopamine (DA) and serotonin (5-HT), which mediate the prokinetic effect of capsaicin, at the L6-S1 levels enhanced colorectal motility in PD rats similarly to that in sham-operated rats. In PD rats, capsaicin enhanced colorectal motility only when a GABA
    MeSH term(s) Humans ; Rats ; Animals ; Parkinson Disease ; Rats, Sprague-Dawley ; Capsaicin/pharmacology ; Serotonin/metabolism ; Brain/metabolism ; Constipation/etiology ; Colorectal Neoplasms ; Oxidopamine
    Chemical Substances Capsaicin (S07O44R1ZM) ; Serotonin (333DO1RDJY) ; Oxidopamine (8HW4YBZ748)
    Language English
    Publishing date 2023-12-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00181.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Essential roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of colorectal motility in rats.

    Sawamura, Tomoya / Yuki, Natsufu / Horii, Kazuhiro / Naitou, Kiyotada / Yamaguchi, Hiroshi / Yamanaka, Akihiro / Shiina, Takahiko / Shimizu, Yasutake

    American journal of physiology. Gastrointestinal and liver physiology

    2023  Volume 324, Issue 6, Page(s) G466–G475

    Abstract: The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic ... ...

    Abstract The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats. hM3Dq or hM4Di was expressed in neurons of the A11 region and/or the raphe nuclei that send output to the lumbosacral defecation center. Immunohistological and functional experiments revealed that both the A11 region and the raphe nuclei directly connected with the lumbosacral spinal cord through descending pathways composed of stimulatory monoaminergic neurons. Stimulation of the hM3Dq-expressing neurons in the A11 region or the raphe nuclei enhanced colorectal motility only when GABAergic transmission in the lumbosacral spinal cord was blocked by bicuculline. Experiments using inhibitory hM4Di-expressing rats revealed that enhancement of colorectal motility caused by noxious stimuli in the colon is mediated by both the A11 region and the raphe nuclei. Furthermore, suppression of the A11 region and/or the raphe nuclei significantly inhibited water avoidance stress-induced defecation. These findings demonstrate that the A11 region and the raphe nuclei play an essential role in the regulation of colorectal motility. This is important because brain regions that mediate both intracolonic noxious stimuli-induced defecation and stress-induced defecation have been clarified for the first time.
    MeSH term(s) Animals ; Rats ; Colorectal Neoplasms ; Medulla Oblongata ; Raphe Nuclei/physiology ; Spinal Cord/physiology
    Language English
    Publishing date 2023-04-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 603840-2
    ISSN 1522-1547 ; 0193-1857
    ISSN (online) 1522-1547
    ISSN 0193-1857
    DOI 10.1152/ajpgi.00019.2023
    Database MEDical Literature Analysis and Retrieval System OnLINE

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