The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure
Jeffrey L. Stock, … , John D. McNeish, Laurent P. Audoly
Jeffrey L. Stock, … , John D. McNeish, Laurent P. Audoly
Published February 1, 2001
Citation Information: J Clin Invest. 2001;107(3):325-331. https://doi.org/10.1172/JCI6749.
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The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure

Abstract

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.

Authors

Jeffrey L. Stock, Katsuhiro Shinjo, John Burkhardt, Marsha Roach, Kana Taniguchi, Toshihisa Ishikawa, Hyung-Suk Kim, Patrick J. Flannery, Thomas M. Coffman, John D. McNeish, Laurent P. Audoly

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The absence of EP1 receptors causes significant changes in cardiovascula...
The absence of EP1 receptors causes significant changes in cardiovascular homeostasis. Resting systolic blood pressure was measured by tail-cuff manometry as described in Methods. Data shown are the average ± SEM (millimeters of mercury) of 5 consecutive days of training followed by 5 consecutive days of measurements. Ten males of each genotype were used for the recordings. (Normal sodium diet: EP1–/–, 111 ± 4 mmHg; EP1+/+, 122 ± 2 mmHg. Low-sodium diet: EP1–/–, 103 ± 4 mmHg; EP1+/+, 111 ± 4 mmHg.) AP < 0.05 Student’s unpaired t test.