The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.

Published

Journal Article

The lipid mediator prostaglandin E2 (PGE2) has diverse biological activity in a variety of tissues. Four different receptor subtypes (EP1-4) mediate these wide-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 PGE2 plays a direct role in mediating algesia and in regulation of blood pressure.

Full Text

Duke Authors

Cited Authors

  • Stock, JL; Shinjo, K; Burkhardt, J; Roach, M; Taniguchi, K; Ishikawa, T; Kim, HS; Flannery, PJ; Coffman, TM; McNeish, JD; Audoly, LP

Published Date

  • February 2001

Published In

Volume / Issue

  • 107 / 3

Start / End Page

  • 325 - 331

PubMed ID

  • 11160156

Pubmed Central ID

  • 11160156

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI6749

Language

  • eng

Conference Location

  • United States