Function of a new form of CYP2B and the inducer structure-inducing activity relationship

1996 Fiscal Year Final Research Report Summary

• Project/Area Number: 07672365
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Kyushu University
• Principal Investigator: YAMADA Hideyuki Kyushu Univ., Fac.of Pharmaceut.Sci., Assoc.Prof., 薬学部, 助教授 (40142351)
• Project Period (FY): 1995 – 1996
• Keywords: Cytochrome P450 / CYP2B subfamily / Strychnos alkaloid / Animal-plant warfare / Hamster / Guinea pig / Rat / Plant toxins

Research Abstract

Our previous study indicated that strychnos alkaloid induces CYP2B3, an ancestral form of CYP2B subfamily. (Yamada et al., Biol.Pharm.Bull., 19,291-293,1996). This observation suggests a possibility that a concept "animal-plant wartfare" plays a role in the evolution of the CYP2B subfamily which can catalyze a number of xenobiotics. One of the objectives of this study was further investigation of above possibility, and twelve toxic ingredients in plants were given to rats and their inducing activity was examined. The results showed that no compounds examined except for cocaine have inducing activity toward CYP2B subfamily including CYP2B3. However, some compounds such as aconitine, nicotine and solanine a little increased other families of cytochrome P450 (P450). These observations suggest that the P450s responsible for plant toxins distribute to not only CYP2B but also other families. Strychnos alkaloid-related compounds ; i.e., ajmaline, pancuromium and gallamine caused the induction of CYP2B3 as well as CYP2B1/2. It is, therefore, evident that structural characteristics seen in strychnine, brucine and related compounds, but not their toxicity is needed for the induction of CYP2B3. A separate experiment was performed to examine species difference on the induction of CYP2B3. As the results, brucine did not cause any induction of the CYP2B subfamily in hamsters, mice and guinea pigs. Other subfamilies of P450 was, however, increased by brucine treatment in these animals. Therefore, the strychnos alkjaloid-induced increase in the content of ancestral form of CYP2B subfamily reported previously was found to be specific for rats. This study suggested that if "animal-plant warfare" is one of the driving forces in the evolution of P450 enzyme, many isoforms in different families would gain xenobiotics-inducibility.