Prostaglanin E2 (PGE2)signaling contributes to each of the manifestations that classically define inflammation--redness, heat and pain. Although non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin are well kown to inhibit this pathway by blocking prostaglandin biosynthesis, more specific agents would be useful, given the disparate biological responses that prostaglanins mediate. Stock et al. now report the genetic disruption of the PGE2 receptor EP1, one of 4 such receptors, is responsible for pain perception and the regulation of blood pressure, 2 of the cardinal physiological responses to PGE2 signaling. The authors find that pained behavior by animals treated to provoke inflammation of the gut is decreased by half in the EP1-/- strain. Remarkably, NSAID treatment causes a similar 50% diminution of such responses in wild type mice and has little or no additional benefit in mutant animals, suggesting that most of the analgesic effect of these drugs can be explained by their inhibition of signaling through this single receptor type.
Stock and colleagues also observe a drop in systolic blood pressure in male mutants, which they attribute to impaired maintenance of the extracellular fluid volume. They also note that other aspects of blood pressure regulation have been found to occur differently in males and females, both in humans and in experimental animals. Thus, although pure EP1 antagonists might prove powerful and relatively specific analgesics, such drugs might also be expected to diminish blood pressure in men.