| Co-Investigator(Kenkyū-buntansha) |
SAITO Muneo Central Institute for Experimental Animals Chief Head, 室長 (50167417)
TERAMOTO Tamio Teikyo University School of Medicine Professor, 医学部, 教授 (20133077)
KAMATAKI Tetsuya University of Hokkaido, Faculty of Pharmaceutical Sciences Professor, 薬学部, 教授 (00009177)
NOMOTO Kikuo Kyushu University, Faculty of Medicine Professor, 医学部, 教授 (50037355)
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| Research Abstract |
Usefulness and advantages/disadvantages of using Suncus murinus as an experiemental animal especially in the field of emesis and motion sickness, lipid metabolism, immune system, carcinogenesis have been investigated in the project. Fundamental data of breeding the animals were also collected. Because of its small body size, this animal is suitable for the screening of various new drugs. Suncus murinus is so far the smallest experimental mammals that have the capability of vomiting. NK1-type neurokinin receptor antagonists were potent antiemetics against a large variety of emetogens, suggesting the involvement of substance P in the emetic reflex. Participation of substance P in emesis was directly demonstrated by the measurement of its release from slices of the dorsal medulla oblongata and by the analysis of pharmacological effects of resiniferatoxin. Analysis of drug metabolizing enzymes in the liver revealed that Suncus murinus lacks Nacetyltransferase and the unique characteristics of CYP2E1. Alcohol dehydrogenase activities in the liver were low in Suncus murinus, which may account for high susceptibility to ethanol in this animal. In order to assess the etiological cause of fatty liver, microsomal triglyhceride transfer protein (MTP) was characterized. Total MTP was very low in this animal, suggesting the defect in assembly of VLDL.A strong correlation between MTP and ACAT was demonstrated. These lines of evidence indicate that Suncus murinus is a unique experimental model useful for researches on emesis, motion sickness, metabolic activity in the liver, fatty liver degeneration and immune system. We cannot obtain these crucial information using the existing animal models.
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