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.
Ohinata
Kousaku
K
Division of Food Bioscience and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan.
Suetsugu
Kentaro
K
Fujiwara
Yoko
Y
Yoshikawa
Masaaki
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015232:Dinoprostone / Q000008:administration & dosage / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004435:Eating; D005215:Fasting; D005746:Gastric Emptying; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000378:metabolism; D051379:Mice; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype
D001786:Blood Glucose; D008738:Methyl Ethers; C461399:ONO-AE1-329; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone