| Project/Area Number |
02557100
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Gunma University |
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Principal Investigator |
ITOH Zen Gunma Univ. Inst. of Endocrinol. Comparative Endocrinology Division Professor, 内分泌研究所・比較内分泌部門, 教授 (00008294)
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| Co-Investigator(Kenkyū-buntansha) |
NIIJIMA Akira Niigata Univ. School of Medicine Dept. of Physiology Professor emeritus, 医学部・生理学教室, 名誉教授 (20018287)
TAKEUCHI Toshiyuki Gunma Univ. Inst. of Endocrinol. Molecular Endocrionology Division Professor, 内分泌研究所・化学構造部門, 教授 (00109977)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 1991: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1990: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | 5-Hydroxytryptamine (5HT) / Serotonin type 3 receptor (5HT_3 receptor) / 5HT_3 antagonist / Interdigestive migrating contraction (IMC) |
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| Research Abstract |
Nausea and vomiting are common side effects of anti-cancer chemotherapeutic drugs. Cisplatin (cis-dichloro-diammineplutinum II), an agent highly effective against a variety of cancers (including testicular, ovarian, urinary-bladder, and head and neck cancers), produces the most severe nausea and emesis of any chemotherapeutic agent Cisplatin is known to cause severe damage on the gastrointestinal tract, along which a highly abandunt population of enterochromaffin (EC) cells containing serotonin (5-Hydroxytryptamine, 5HT) are located. 5HT released from EC cells appears to stimulate its receptors on the afferent nerve endings of Vagus that transmits the stimulus caused by 5HT to the area postrema (AP) of the medulla oblongata. The AP is thought to act as a chemoreceptor trigger zone for nausea and emesis. The stimulus triggered by the AP travels through the efferent nerve of Vagus to cause vomiting reflex in the gastrointestinal tract. Recently investigations performed in laboratory anim
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als have revealed that selective antagonists of serotonin S3 (5HT_3) receptors prevent the vomiting induced by cisplatin. However the effect of 5HT_3 antagonist to prevent vomiting reaction in the gastrointestinal tract is unclear. Thus we utilized dogs implanted with force transducers onto the serosa of the gastrointestinal tract in a direction to measure circular muscle contraction, and observed the effect of a series of 5HT_3 antagonists including ICS205-930, BRL43694 and GR38032F. The appearance of phase III interdigestive migrating contractions (IMC) in the gastrointestinal tract is thought to be caused by rhythmicoscillations of circulating motilin levels with peaks occuring every 90-120 min. Infusion of 5HT_3 antagonists prevented the appearance of IMC in the stomach, but not that of IMC in the intestine. However, the disappearance of IMC by 5HT_3 antagonists was not observed in the denervated stomach, indicating that 5HT_3 antagonists prevent the transmission of 5HT stimulus through the afferent nerve of Vagus. Less
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