First Author | Stock JL | Year | 2001 |
Journal | J Clin Invest | Volume | 107 |
Issue | 3 | Pages | 325-31 |
PubMed ID | 11160156 | Mgi Jnum | J:79387 |
Mgi Id | MGI:2387960 | Doi | 10.1172/JCI6749 |
Citation | Stock JL, et al. (2001) The prostaglandin E2 EP1 receptor mediates pain perception and regulates blood pressure. J Clin Invest 107(3):325-31 |
abstractText | 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. |