The house musk shrew (Suncus murinus):: a unique animal with extremely low level of expression of mRNAs for CYP3A and flavin-containing monooxygenase

被引:4
作者
Mushiroda, T
Yokoi, T
Itoh, K
Nunoya, K
Nakagawa, T
Kubota, M
Takahara, E
Nagata, O
Kato, H
Kamataki, T
机构
[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Div Pharmacobiodynam, Lab Drug Metab,Kita Ku, Sapporo, Hokkaido 0600812, Japan
[2] Hokuriku Seiyaku Co, Div Res & Dev, Fukui 9118555, Japan
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY | 2000年 / 126卷 / 03期
关键词
cytochrome P450; flavin-containing monooxygenase; aryl sulfotransferase; UDP-glucuronosyltransferase; glutathione S-transferase; carboxy esterase; microsomal epoxide hydrolase; Northern blot;
D O I
10.1016/S0742-8413(00)00113-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Expression of drug-metabulizing enzymes including cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) in various tissues of Suncus murinus (Suncus) were examined. Northern blot analysis showed that mRNAs hybridizable with cDNAs for rat CYP1A2, human CYP2A6, rat CYP2B1, human CYP2C8, human CYP2D6, rat CYP2E1, human CYP3A4 and rat CYP3A1 were expressed in various tissues from Suncus. The mRNA level of CYP2A in the Suncus lung was very high. Furthermore, it was found that the level of CYP2A mRNA in thr Suncus lung was higher compared to the Suncus liver. The expression level of mRNA hybridizable with cDNA for human CYP3A4 was very low. The presence of CYP3A gene in Suncus was proven by the induction of the CYP with dexamethasone. Very low expression levels of mRNAs hybridizable with cDNAs for rat FMO1, rat FMO2, rat FMO3 and rat FMO5 were also seen in Suncus liver. No apparent hybridization band appeared when human FMO4 cDNA was used as a probe. The hepatic expression of mRNAs hybridizable with cDNAs for UDP-glucuronosyltransferase 1*6, aryl sulfotransferase, glutathione S-transferase 1, carboxyesterase and microsomal epoxide hydrolase in the Suncus were observed. These results indicate that the Suncus is a unique animal species in that mRNAs for CYP3A and FMO are expressed at very low Levels. (C) 2000 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:225 / 234
页数:10
相关论文
共 51 条
  • [1] A GENETIC-POLYMORPHISM OF THE N-OXIDATION OF TRIMETHYLAMINE IN HUMANS
    ALWAIZ, M
    AYESH, R
    MITCHELL, SC
    IDLE, JR
    SMITH, RL
    [J]. CLINICAL PHARMACOLOGY & THERAPEUTICS, 1987, 42 (05) : 588 - 594
  • [2] The pharmacology of the emetic response to upper gastrointestinal tract stimulation in Suncus murinus
    Andrews, P
    Torii, Y
    Saito, H
    Matsuki, N
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 307 (03) : 305 - 313
  • [3] [Anonymous], 1989, SYNTHETIC OLIGONUCLE
  • [4] THE FISH ODOR SYNDROME - BIOCHEMICAL, FAMILIAL, AND CLINICAL ASPECTS
    AYESH, R
    MITCHELL, SC
    ZHANG, A
    SMITH, RL
    [J]. BRITISH MEDICAL JOURNAL, 1993, 307 (6905) : 655 - 657
  • [5] Ayesh R, 1988, BR J CLIN PHARM, V25, P664
  • [6] ASSESSMENT OF LIVER METABOLIC FUNCTION - CLINICAL IMPLICATIONS
    BROCKMOLLER, J
    ROOTS, I
    [J]. CLINICAL PHARMACOKINETICS, 1994, 27 (03) : 216 - 248
  • [7] ROLE OF HEPATIC FLAVIN-CONTAINING MONOOXYGENASE-3 IN DRUG AND CHEMICAL METABOLISM IN ADULT HUMANS
    CASHMAN, JR
    PARK, SB
    BERKMAN, CE
    CASHMAN, LE
    [J]. CHEMICO-BIOLOGICAL INTERACTIONS, 1995, 96 (01) : 33 - 46
  • [8] CHIRGWIN JM, 1979, BIOCHEMISTRY-US, V18, P5299
  • [9] DEBAUN JR, 1970, CANCER RES, V30, P577
  • [10] THE HUMAN-LIVER GLUTATHIONE S-TRANSFERASE GENE SUPERFAMILY - EXPRESSION AND CHROMOSOME MAPPING OF AN HB SUBUNIT CDNA
    DEJONG, JL
    CHANG, CM
    WHANGPENG, J
    KNUTSEN, T
    TU, CPD
    [J]. NUCLEIC ACIDS RESEARCH, 1988, 16 (17) : 8541 - 8554