期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 107, 期 3, 页码 325-331出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI6749
关键词
-
The lipid mediator prostaglandin E2 (PGE(2)) has diverse biological activity in a variety of tissues, Four different receptor subtypes (EP1-4) mediate these nide-ranging effects. The EP-receptor subtypes differ in tissue distribution, ligand-binding affinity, and coupling to intracellular signaling pathways. To identify the physiological roles for one of these receptors, the EP1 receptor, we generated EP1-deficient (EP1(-/-)) mice using homologous recombination in embryonic stem cells derived from the DBA/1lacJ strain of mice. The EP1(-/-) mice are healthy and fertile, without any overt physical defects. However, their pain-sensitivity responses, tested in two acute prostaglandin-dependent models, were reduced by approximately 50%. This reduction in the perception of pain was virtually identical to that achieved through pharmacological inhibition of prostaglandin synthesis in wild-type mice using a cyclooxygenase inhibitor. In addition, systolic blood pressure is significantly reduced in EP1 receptor-deficient mice and accompanied by increased renin-angiotensin activity especially in males, suggesting a role for this receptor in cardiovascular homeostasis. Thus, the EP1 receptor for PGE(2) plays a direct role in mediating algesia and in regulation of blood pressure.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据