CHARACTERIZATION OF A UGT FOR MORPHINE 6 GLUCURONIDE

描述：（申请人摘要） 申请人的长期目标是成为一名医生-科学家 在新生儿药理学方面有专长 为了实现这一目标，她 组建了一个由生理学系的导师团队， 俄勒冈州健康科学药理学和儿科系 大学（OHSU），由：药理学家与专业知识， 药物滥用领域和吗啡代谢;儿科医生熟练的 最新的分子和遗传技术;药理学家谁是专家 在蛋白质化学和药物代谢;和分子内分泌学家 在分子生物学领域有20多年的经验 此外，OHSU 提供了一个强大的研究环境，申请人可以追求她 目标. 该研究项目的总体目标是描述几内亚 猪UDP-葡萄糖醛酸基转移酶（UGT），代谢吗啡， 吗啡-6-葡糖苷酸，其活性代谢物。 这种代谢产物是由 人类，豚鼠和兔子，但不是更频繁的研究， 大鼠 有相当多的证据表明， 吗啡-6-葡萄糖醛酸苷不同于那些产生 非镇痛代谢物，吗啡-3-葡糖苷酸。 特征将 包括蛋白质的纯化，cDNA的鉴定，和 阐明了这种植物的个体发育和组织分布 葡萄糖醛酸转移酶 吗啡-6-葡萄糖醛酸苷产生的 转移酶是一种更有效的镇痛剂和呼吸抑制剂， 母体吗啡 因此，在药物滥用领域， 了解这类动物的组织分布和个体发育， 葡萄糖醛酸转移酶 在为《公约》作出贡献的过程中， 了解吗啡代谢，研究者将获得 多维教育，使她能够作为一个独立的 新生儿药理学研究者，具有临床和 基础研究

DESCRIPTION: (Applicant's Abstract) The long-term objective of the applicant is to become a physician-scientist with expertise in Neonatal Pharmacology. To achieve that goal she has assembled a team of mentors from the Departments of Physiology and Pharmacology and the Department of Pediatrics at Oregon Health Sciences University (OHSU) that consists of: a Pharmacologist with expertise in the drug abuse field and morphine metabolism; a Pediatrician skilled in the latest molecular and genetic techniques; a Pharmacologist who is an expert in protein chemistry and drug metabolism; and a Molecular Endocrinologist with over 20 years experience in molecular biology. In addition, OHSU provides a strong research environment in which the applicant can pursue her goals. The overall goal of the research project is to characterize a guinea pig UDP-glucuronosyltransferase (UGT) that metabolizes morphine to morphine-6-glucuronide, its active metabolite. This metabolite is produced by humans, guinea pigs and rabbits, but not by the more frequently-studied rat. There is considerable evidence that the UGT that produces morphine-6-glucuronide is different from those that produce the non-analgesic metabolite, morphine-3-glucuronide. The characterization will consist of purification of the protein, identification of the cDNA, and elucidation of the ontogeny and tissue distribution of this glucuronosyltransferase. The morphine-6-glucuronide produced by this transferase is a more potent analgesic and respiratory depressant than the parent morphine. It is, therefore, important in the drug abuse field to understand the tissue distribution and ontogeny of this glucuronosyltransferase. In the process of contributing to the understanding of morphine metabolism, the investigator will acquire a multidimensional education that will allow her to function as an independent investigator in neonatal pharmacology with expertise in both clinical and basic research.