Activation of prostaglandin E receptor EP4 subtype suppresses food intake in mice.

Prostaglandin (PG) E2, a bioactive lipid produced in the brains of various mammals, decreases food intake after central administration. We examined which of four distinct subtypes of PGE2 receptors (EP1-EP4) mediated the anorexigenic action of PGE2 using highly selective ligands. PGE2 at a dose of 0.1-10 nmol/mouse decreased food intake after intracerebroventricular (i.c.v.) administration in a dose-dependent manner in fasted mice. A centrally administered EP4 agonist, ONO-AE1-329 at a dose of 1-10 nmol/mouse mimicked the anorexigenic action by PGE2. The anorexigenic action of PGE2 or EP4 agonist was ameliorated by EP4 antagonist ONO-AE3-208 at a dose of 10 nmol/mouse. Thus, activation of PGE2-EP4 signaling in the central nervous system suppresses food intake. The EP4 agonist at a dose of 10 nmol/mouse delayed gastric emptying and elevated blood glucose.