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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
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Article ; Online: Suncus murinus as a novel model animal that is suitable for elucidating the mechanism of daily torpor.

Horii, Yuuki / Okadera, Kanako / Miyawaki, Shingo / Shiina, Takahiko / Shimizu, Yasutake

Biomedical research (Tokyo, Japan)

2022 Volume 43, Issue 2, Page(s) 53–57

Abstract: Torpor, a state of lowered body temperature due to active reduction of the metabolic rate, has potential medical benefits. The aim of this study was to establish a novel laboratory animal that enter torpor without imposing complex conditions. When house ... ...

Abstract	Torpor, a state of lowered body temperature due to active reduction of the metabolic rate, has potential medical benefits. The aim of this study was to establish a novel laboratory animal that enter torpor without imposing complex conditions. When house musk shrews (Suncus murinus) were kept at an ambient temperature of 24°C, most of the animals did not enter daily torpor. However, when the ambient temperature was lowered to below 20°C, all of the shrews showed torpor in the absence of fasting and short-day photoperiod. The shrews that were exposed to a stepwise decrease in ambient temperature from 24°C to 8°C entered torpor even after returning them to a room kept at 24°C. In conclusion, this study indicates that Suncus murinus may be a suitable model animal for elucidating the mechanism of daily torpor. Elucidation of the mechanisms of torpor by using this model may be useful for inducing a state of artificial hibernation in various species including humans.
MeSH term(s)	Animals ; Body Temperature ; Hibernation ; Photoperiod ; Shrews ; Torpor
Language	English
Publishing date	2022-03-24
Publishing country	Japan
Document type	Journal Article
ZDB-ID	604561-3
ISSN	1880-313X ; 0388-6107
ISSN (online)	1880-313X
ISSN	0388-6107
DOI	10.2220/biomedres.43.53
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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
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Article ; Online: Successful induction of deep hypothermia by isoflurane anesthesia and cooling in a non-hibernator, the rat.

Shimaoka, Hiroki / Shiina, Takahiko / Suzuki, Hayato / Horii, Yuuki / Horii, Kazuhiro / Shimizu, Yasutake

The journal of physiological sciences : JPS

2021 Volume 71, Issue 1, Page(s) 10

Abstract: The aim of the present study was to establish a novel method for inducing deep hypothermia in rats. Cooling rats anesthetized with isoflurane caused a time-dependent decrease in rectal temperature, but cardiac arrest occurred before their body ... ...

Abstract	The aim of the present study was to establish a novel method for inducing deep hypothermia in rats. Cooling rats anesthetized with isoflurane caused a time-dependent decrease in rectal temperature, but cardiac arrest occurred before their body temperature reached 20 °C when isoflurane inhalation was continued during the cooling process. Stopping inhalation of isoflurane when the rectal temperature reached 22.5 °C successfully induced deep hypothermia, although stopping the inhalation at 27.5 °C resulted in spontaneous recovery of rectal temperature. The hypothermic condition was able to be maintained for up to 6 h. A large number of c-Fos-positive cells were detected in the hypothalamus during hypothermia. Both the maintenance of and recovery from hypothermia caused organ injury, but the damage was transient and recovered within 1 week. These findings indicate that the established procedure is appropriate for inducing deep hypothermia without accompanying serious organ injury in rats.
MeSH term(s)	Anesthetics, Inhalation/pharmacology ; Animals ; Antihypertensive Agents/pharmacology ; Cold Temperature ; Gene Expression Regulation/drug effects ; Heart Rate ; Hexamethonium/pharmacology ; Hypothermia/chemically induced ; Isoflurane/pharmacology ; Male ; Proto-Oncogene Proteins c-fos/genetics ; Proto-Oncogene Proteins c-fos/metabolism ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Anesthetics, Inhalation ; Antihypertensive Agents ; Proto-Oncogene Proteins c-fos ; Hexamethonium (3C9PSP36Z2) ; Isoflurane (CYS9AKD70P)
Language	English
Publishing date	2021-03-30
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/s12576-021-00794-1
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Article: The Mechanism Enabling Hibernation in Mammals.

Horii, Yuuki / Shiina, Takahiko / Shimizu, Yasutake

Advances in experimental medicine and biology

2018 Volume 1081, Page(s) 45–60

Abstract: Some rodents including squirrels and hamsters undergo hibernation. During hibernation, body temperature drops to only a few degrees above ambient temperature. The suppression of whole-body energy expenditure is associated with regulated, but not passive, ...

Abstract	Some rodents including squirrels and hamsters undergo hibernation. During hibernation, body temperature drops to only a few degrees above ambient temperature. The suppression of whole-body energy expenditure is associated with regulated, but not passive, reduction of cellular metabolism. The heart retains the ability to beat constantly, although body temperature drops to less than 10 °C during hibernation. Cardiac myocytes of hibernating mammals are characterized by reduced Ca
MeSH term(s)	Alternative Splicing ; Animals ; Calcium Signaling ; Cold Temperature ; Energy Metabolism ; Gene Expression Regulation ; Heart/physiology ; Hibernation ; Myocardium/metabolism ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Species Specificity
Chemical Substances	RNA-Binding Proteins
Language	English
Publishing date	2018-10-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-13-1244-1_3
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Article ; Online: Mild hypothermia causes a shift in the alternative splicing of cold-inducible RNA-binding protein transcripts in Syrian hamsters.

Horii, Yuuki / Shimaoka, Hiroki / Horii, Kazuhiro / Shiina, Takahiko / Shimizu, Yasutake

American journal of physiology. Regulatory, integrative and comparative physiology

2019 Volume 317, Issue 2, Page(s) R240–R247

Abstract: Cold-shock proteins are thought to participate in the cold-tolerant nature of hibernating animals. We previously demonstrated that an alternative splicing may allow rapid induction of functional cold-inducible RNA-binding protein (CIRBP) in the hamster ... ...

Abstract	Cold-shock proteins are thought to participate in the cold-tolerant nature of hibernating animals. We previously demonstrated that an alternative splicing may allow rapid induction of functional cold-inducible RNA-binding protein (CIRBP) in the hamster heart. The purpose of the present study was to determine the major cause of the alternative splicing in Syrian hamsters. RT-PCR analysis revealed that CIRBP mRNA is constitutively expressed in the heart, brain, lung, liver, and kidney of nonhibernating euthermic hamsters with several alternative splicing variants. In contrast, the short variant containing an open-reading frame for functional CIRBP was dominantly found in the hibernating animals. Keeping the animals in a cold and dark environment did not cause a shift in the alternative splicing. Induction of hypothermia by central administration of an adenosine A
MeSH term(s)	Acclimatization/physiology ; Alternative Splicing/genetics ; Animals ; Body Temperature/genetics ; Body Temperature/physiology ; Cold Temperature ; Heart/physiology ; Hibernation/genetics ; Hibernation/physiology ; Hypothermia/physiopathology ; Male ; RNA, Messenger/metabolism ; RNA-Binding Proteins/metabolism
Chemical Substances	RNA, Messenger ; RNA-Binding Proteins
Language	English
Publishing date	2019-06-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00012.2019
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Article ; Online: Hypothermia induces changes in the alternative splicing pattern of cold-inducible RNA-binding protein transcripts in a non-hibernator, the mouse.

Horii, Yuuki / Shiina, Takahiko / Uehara, Saki / Nomura, Kanako / Shimaoka, Hiroki / Horii, Kazuhiro / Shimizu, Yasutake

Biomedical research (Tokyo, Japan)

2019 Volume 40, Issue 4, Page(s) 153–161

Abstract: Cold-inducible RNA-binding protein (CIRBP) plays important roles in protection against harmful effects of cold temperature. We previously found that several splicing variants of CIRBP mRNA are constitutively expressed in the heart of non-hibernating ... ...

Abstract	Cold-inducible RNA-binding protein (CIRBP) plays important roles in protection against harmful effects of cold temperature. We previously found that several splicing variants of CIRBP mRNA are constitutively expressed in the heart of non-hibernating euthermic hamsters and that one of the variants is predominantly expressed with remarkable reduction in the expression of other variants in hibernating hypothermic hamsters. The aim of this study was to determine whether the regulation of alternative splicing is a common function in a non-hibernator, the mouse. The expression of CIRBP mRNA was assessed by RT-PCR. In euthermic control mice, several splicing variants of CIRBP mRNA were detected in various organs. When hypothermia was induced in mice by using isoflurane anesthesia, the short form variant, which encodes full-length functional CIRBP, was predominantly detected. Keeping body temperature of anesthetized mice at 37°C prevented changes in the splicing pattern. Exposure of mice to a low temperature did not change the splicing pattern, suggesting that endogenous neuronal and/or humoral pathways activated in response to cold stimuli applied to the body surface play minor roles. In agreement with this, the shift in alternative splicing was reproduced in isolated leukocytes in vitro when they were incubated at 28°C. Since application of a TRPM8 or TRPA1 agonist at 37°C failed to promote the shift in the splicing pattern, it seems likely that cold-sensitive channels are not involved in the splicing regulation. Therefore, it is probable that a substantial reduction of temperature is a major cause of the regulation of alternative splicing of CIRBP transcripts. The regulatory system of CIRBP expression at the level of alternative splicing, which was originally discovered in the hibernating hamster, commonly exists in non-hibernators such as mice.
MeSH term(s)	Alternative Splicing ; Animals ; Body Temperature ; Cricetinae ; Fever/chemically induced ; Fever/metabolism ; Fever/pathology ; Hibernation ; Male ; Mice ; RNA, Messenger/biosynthesis ; RNA-Binding Proteins/biosynthesis
Chemical Substances	Cirbp protein, mouse ; RNA, Messenger ; RNA-Binding Proteins
Language	English
Publishing date	2019-08-14
Publishing country	Japan
Document type	Journal Article
ZDB-ID	604561-3
ISSN	1880-313X ; 0388-6107
ISSN (online)	1880-313X
ISSN	0388-6107
DOI	10.2220/biomedres.40.153
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Article ; Online: Sexually dimorphic response of colorectal motility to noxious stimuli in the colorectum in rats.

Horii, Kazuhiro / Ehara, Yuka / Shiina, Takahiko / Naitou, Kiyotada / Nakamori, Hiroyuki / Horii, Yuuki / Shimaoka, Hiroki / Saito, Shouichiro / Shimizu, Yasutake

The Journal of physiology

2020 Volume 599, Issue 5, Page(s) 1421–1437

Abstract: Key points: This study showed a remarkable sex difference in responses of colorectal motility to noxious stimuli in the colorectum in rats: colorectal motility was enhanced in response to intracolonic administration of a noxious stimulant, capsaicin, in ...

Abstract	Key points: This study showed a remarkable sex difference in responses of colorectal motility to noxious stimuli in the colorectum in rats: colorectal motility was enhanced in response to intracolonic administration of a noxious stimulant, capsaicin, in male rats but not in female rats. The difference in descending neurons from the brain to spinal cord operating after noxious stimulation could be responsible for the sex difference. In male rats, serotoninergic and dopaminergic neurons are dominantly activated, both of which activate the spinal defaecation centre. In female rats, GABAergic neurons in addition to serotoninergic neurons are activated. GABA may compete for facilitative action of 5-HT in the spinal defaecation centre, and thereby colorectal motility is not enhanced in response to intracolonic administration of capsaicin. The findings provide a novel insight into pathophysiological mechanisms of sex differences in functional defaecation disorders such as irritable bowel syndrome. Abstract: We previously demonstrated that noxious stimuli in the colorectum enhance colorectal motility through activation of descending pain inhibitory pathways in male rats. It can be expected that the regulatory mechanisms of colorectal motility differ in males and females owing to remarkable sex differences in descending pain inhibitory pathways. Thus, we aimed to clarify sex differences in responses of colorectal motility to noxious stimuli in rats. Colorectal motility was measured in vivo in anaesthetized rats. Administration of a noxious stimulant, capsaicin, into the colorectal lumen enhanced colorectal motility in male rats but not in female rats. Quantitative PCR and immunohistochemistry showed that TRPV1 expression levels in the dorsal root ganglia and in the colorectal mucosa were comparable in male and female rats. When a GABA
MeSH term(s)	Animals ; Capsaicin/pharmacology ; Colorectal Neoplasms ; Female ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord
Chemical Substances	Capsaicin (S07O44R1ZM)
Language	English
Publishing date	2020-12-28
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP279942
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Article ; Online: Characterization of peristaltic motility in the striated muscle portion of the esophagus using a novel in vivo method in rats.

Horii, Kazuhiro / Shiina, Takahiko / Naitou, Kiyotada / Nakamori, Hiroyuki / Horii, Yuuki / Shimaoka, Hiroki / Shimizu, Yasutake

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society

2018 Volume 31, Issue 4, Page(s) e13518

Abstract: Background: Esophageal peristalsis is controlled by the brainstem via vago-vagal reflex. However, the precise regulatory mechanisms in the striated muscle portion are largely unknown. The aim of this study was to characterize peristaltic motility in the ...

Abstract	Background: Esophageal peristalsis is controlled by the brainstem via vago-vagal reflex. However, the precise regulatory mechanisms in the striated muscle portion are largely unknown. The aim of this study was to characterize peristaltic motility in the portion of the esophagus using a novel in vivo method in rats. Methods: A balloon-tipped catheter was placed in the esophagus of a rat anesthetized with urethane. To induce esophageal peristalsis, the balloon was inflated by water injection. Key results: When the balloon was inflated near the bronchial bifurcation, the balloon was transported in the aboral direction. Vagotomy abolished the peristaltic response. The threshold volume for inducing esophageal peristalsis varied according to the velocity of balloon distention; the volume being effective to induce peristalsis at a low inflation speed was smaller than the threshold volume at a rapid inflation speed. Even in the absence of inflation, keeping the balloon inside the esophagus during an interval period prevented subsequent induction of peristaltic motility. In addition, a nitric oxide synthase inhibitor abolished the induction of esophageal peristalsis. Conclusions and inferences: Our findings suggest that (a) in addition to the intensity, the velocity of distention is important for activating the mechanosensory mechanism to induce esophageal peristalsis, (b) tonic inputs from afferent fibers located at the mucosa may reduce the excitability of mechanosensors which is necessary for inducing peristalsis, and (c) nitric oxide plays essential roles in the induction of esophageal peristalsis. These results provide novel insights into the regulatory mechanisms of esophageal motility.
MeSH term(s)	Animals ; Catheterization ; Deglutition/physiology ; Esophagus/physiology ; Male ; Muscle, Striated/physiology ; Peristalsis/physiology ; Rats ; Rats, Sprague-Dawley ; Vagotomy ; Vagus Nerve
Language	English
Publishing date	2018-12-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.13518
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Article ; Online: Roles of the noradrenergic nucleus locus coeruleus and dopaminergic nucleus A11 region as supraspinal defecation centers in rats.

Nakamori, Hiroyuki / Naitou, Kiyotada / Horii, Yuuki / Shimaoka, Hiroki / Horii, Kazuhiro / Sakai, Hiroki / Yamada, Akihiro / Furue, Hidemasa / Shiina, Takahiko / Shimizu, Yasutake

American journal of physiology. Gastrointestinal and liver physiology

2019 Volume 317, Issue 4, Page(s) G545–G555

Abstract: We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from ...

Abstract	We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles of the noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the defecation reflex. Colorectal motility was measured with a balloon in anesthetized rats. Electrical stimulation of the LC and A11 region increased colorectal pressure only when a GABA
MeSH term(s)	Adrenergic alpha-1 Receptor Antagonists/pharmacology ; Animals ; Colon/drug effects ; Colon/physiology ; Defecation/physiology ; Dopamine/physiology ; Dopamine Agonists/pharmacology ; Electric Stimulation ; Gastrointestinal Motility ; Locus Coeruleus/physiology ; Lumbosacral Region/innervation ; Lumbosacral Region/physiology ; Male ; Norepinephrine/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Dopamine D2/drug effects ; Rectum/drug effects ; Rectum/physiology ; Spinal Cord/physiology ; Sympathetic Nervous System/physiology
Chemical Substances	Adrenergic alpha-1 Receptor Antagonists ; Dopamine Agonists ; Receptors, Dopamine D2 ; Dopamine (VTD58H1Z2X) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2019-08-28
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.00062.2019
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