Physiological and Pathophysiological roles of prostanoids revealed from studies using mice lacking their receptors

使用缺乏受体的小鼠进行的研究揭示了前列腺素的生理和病理生理作用

• 批准号: 11694269
• 负责人: USHIKUBI Fumitaka
• 金额: $ 4.22万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11694269/
• 关键词: prostanoids; prostaglandin; knockout mice; prostanoid receptor; fertilization; allergic asthma; platelets; ischemia-reperfusipn; トロンボキサン; 中枢神経機能; 肺高血圧症; 気管支喘息; 大腸癌

The prostanoids are lipid mediators showing variable effects on many organs. Theirphysiological and pathophysiological roles in the body, however, have been largely unknown. We attmpted to clarify these roles using mice lacking the prostanoids receptors individually, and found several novel and important roles of prostanoids. They include a cardioprotective role of prostaglandin (PG)l_2 in ischemia-reperfusion injury, roles of PGE_2 via the EP_3 receptor in hemostasis, thromboembolism and alkari secretion in the duodenum, a role of PGD_2 as a mediator of allergic asthma, participation of PGE_2 via the EP_1 and EP_2 receptors in the carcinogenesis of colon, a regulatory role of PGE_2 via the EP_2 receptor of ovulation ad fertilization and a role of PGE_2 via the EP_4 receptor in bone resorption. Furthermore, other roles of prostanoids have been being clarified in many systems, such as central nervous, immune, cardiovascular and gastrointestinal systems. These results would contribute to the development of novel drugs able to control many pathological conditions, in which prostanoids have major roles.

前列腺素类是脂质介质，对许多器官表现出不同的影响。然而，它们在体内的生理和病理生理作用在很大程度上是未知的。我们尝试用前列腺素受体缺失的小鼠来阐明这些作用，并发现了前列腺素的一些新的和重要的作用。包括前列腺素（PG）1_2在缺血再灌注损伤中的心脏保护作用、PGE_2通过EP_3受体在止血、血栓栓塞和十二指肠碱分泌中的作用、PGD_2作为过敏性哮喘介质的作用、PGE_2通过EP_1和EP_2受体参与结肠癌的发生、PGE_2通过EP_2受体调节排卵和受精; PGE_2通过EP_4受体调节骨吸收。此外，前列腺素类化合物在许多系统中的其他作用已经被阐明，例如中枢神经系统、免疫系统、心血管系统和胃肠道系统。这些结果将有助于开发能够控制许多病理条件的新药，其中前列腺素类化合物具有重要作用。

项目成果

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