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

Publication ,  Journal Article
Stock, JL; Shinjo, K; Burkhardt, J; Roach, M; Taniguchi, K; Ishikawa, T; Kim, HS; Flannery, PJ; Coffman, TM; McNeish, JD; Audoly, LP
Published in: J Clin Invest
February 2001

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.

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Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

February 2001

Volume

107

Issue

3

Start / End Page

325 / 331

Location

United States

Related Subject Headings

  • Uterus
  • Receptors, Prostaglandin E, EP1 Subtype
  • Receptors, Prostaglandin E
  • RNA, Messenger
  • Piroxicam
  • Pain Threshold
  • Mutation
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice
 

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Stock, J. L., Shinjo, K., Burkhardt, J., Roach, M., Taniguchi, K., Ishikawa, T., … Audoly, L. P. (2001). The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J Clin Invest, 107(3), 325–331. https://doi.org/10.1172/JCI6749
Stock, J. L., K. Shinjo, J. Burkhardt, M. Roach, K. Taniguchi, T. Ishikawa, H. S. Kim, et al. “The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.J Clin Invest 107, no. 3 (February 2001): 325–31. https://doi.org/10.1172/JCI6749.
Stock JL, Shinjo K, Burkhardt J, Roach M, Taniguchi K, Ishikawa T, et al. The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J Clin Invest. 2001 Feb;107(3):325–31.
Stock, J. L., et al. “The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure.J Clin Invest, vol. 107, no. 3, Feb. 2001, pp. 325–31. Pubmed, doi:10.1172/JCI6749.
Stock JL, Shinjo K, Burkhardt J, Roach M, Taniguchi K, Ishikawa T, Kim HS, Flannery PJ, Coffman TM, McNeish JD, Audoly LP. The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J Clin Invest. 2001 Feb;107(3):325–331.

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

February 2001

Volume

107

Issue

3

Start / End Page

325 / 331

Location

United States

Related Subject Headings

  • Uterus
  • Receptors, Prostaglandin E, EP1 Subtype
  • Receptors, Prostaglandin E
  • RNA, Messenger
  • Piroxicam
  • Pain Threshold
  • Mutation
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice