| Project/Area Number |
61480426
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
KAMATAKI Tetsuya Faculty of pharmaceutical Sciemces, Hokkaido University, 薬学部, 教授 (00009177)
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| Co-Investigator(Kenkyū-buntansha) |
KOMORI Masayuki Faculy of Pharmaceutical Sciences,Hokkaido University (Hashimoto,Ma), 薬学部, 助手 (40183347)
MIURA Tishaki Faculy of Pharmaceutical Sciences, Hokkaido University, 薬学部, 助教授 (10091505)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1987: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1986: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | drug metabolism / sex differende / species difference / cytochrome P-450 / クローニング / テストステロン |
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| Research Abstract |
In previous studies, we clarified that the occurrence of the sex-related differences in the actions and toxidities of drugs and toxicants could be accounted for by the presence of sex-specific forms of cytochrome P450(P-450-male and P-450-female) inliver microsomes of rats. Thus, the purpose of this research was to examine the possibility of whether are forms of cytochrome P-450 with properties similar to P-450-male in microsomes of other animal species including humans. The function of the forms of cytochrome P-450 was also studied.
During the course of this research projects, we obtained results as follows; 1) Proteins immunochemically reactive with anti-P-450-male antibodies were present in liver microsomes of all animals examinned. The activities of hydroxylases of testosterone, varied animal species, indicating that the functions of cytochrome P-450 related to P-450-male were not necessarily identical among animals. 2)In the first evidence that hamster showed significant sex differences in the population of cytochrome P-450 as well as the activities of testosterone hydroxylases. These were regulated by groth hormone. 3)Forms of cytochrome P-450 immunochemically related to P-450-male, which were purified from liver microsomes of beagle dogs, showed drug oxidation activities in a similar fashion but differed with each other in steroid hydroxylations. 4)A cDNA clone with sequences homologous to P-450-male were obtained and expressed in yeast.
In conclusion, this research project was completed along with the proposedule, but to much higher extsnts.
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