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

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 pa...

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Bibliographic Details
Published in:The Journal of clinical investigation 2001-02, Vol.107 (3), p.325-331
Main Authors: Stock, J L, Shinjo, K, Burkhardt, J, Roach, M, Taniguchi, K, Ishikawa, T, Kim, H S, Flannery, P J, Coffman, T M, McNeish, J D, Audoly, L P
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Blood Pressure - physiology
Enzyme Inhibitors - pharmacology
Female
Heterozygote
Kidney - metabolism
Lung - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mutation
Pain Threshold - physiology
Piroxicam - pharmacology
Receptors, Prostaglandin E - deficiency
Receptors, Prostaglandin E - genetics
Receptors, Prostaglandin E - physiology
Receptors, Prostaglandin E, EP1 Subtype
RNA, Messenger - analysis
Uterus - metabolism
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Summary: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.
ISSN:0021-9738
1558-8238
DOI:10.1172/jci6749