| 研究実績の概要 |
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by recurrent abdominal pain and abnormal bowel patterns. Little is known about neurotransmitter and neuromodulator which crucially regulate the pathophysiology of IBS. The aim of this study was to determine the neurotransmitter and neuromodulator including 5-hydroxytryptamine (5-HT) and corticotropin-releasing hormone (CRH) in IBS.
We made rat model of IBS with colorectal distention (CRD). CRD was performed with computerized barostat system and visceral sensitivity was evaluated with visceromotor response (VMR) by electromyogram. We made the experimental system for testing neurotransmission modulated by administration of vehicle, CRH agonist, CRH antagonist, 5-HT4 agonist, selective serotonin repute inhibitor (SSRI), and their combination.
We made the experimental system to extend the experiment to the other neurotransmitters and neuromodulators and their receptors. It included morphological changes of the neurons and the glia cells as well as microdialysis in the brain and the gut of IBS model. Quantification of the data, statistical analyses, and writing manuscripts were prepared.
We required the maximum amount of the grant by the following reasons; 1) We needed new experimental kits for the assay, 2) We needed multiple experiments to determine statistically optimal doses of CRH agonist, CRH antagonist, 5-HT4 agonist and SSRI, 3) CRH receptor, 5-HT4 receptor and SERT are highly possible to play crucial roles in the pathogenesis of IBS.
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| 今後の研究の推進方策 |
We would like to use novel CRH agonists and antagonists to test the function of CRH system relating brain-gut interactions. Animal housing, visceral perception equipment, animal behavior testing, and brain-gut tissue examination system were well developed.
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