Central prostaglandin D2 exhibits anxiolytic-like activity via the DP1 receptor in mice |
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| Authors: | Hui Zhao Kousaku Ohinata Masaaki Yoshikawa |
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| Affiliation: | 1. Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan;2. Fronteir Research Center, Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan;3. CREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan;1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;2. Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;3. The Bert W. Strassburger Lipid Center, Tel Aviv University, 52621 Hashomer Tel, Israel;4. Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, 52621 Hashomer Tel, Israel;5. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, United States;1. Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;2. Department of Mediator and Signal Transduction Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;3. Department of Anatomy, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan;4. Department of Matrix Biology and Regenerative Medicine, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;1. Department of Pharmaceutical Health Chemistry, Institute of Biomedical Sciences, Tokushima University Graduate School, Shomachi, Tokushima 770-8505, Japan;2. Department of Medical Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Shomachi, Tokushima 770-8505, Japan;3. Faculty of Pharmacy, Yasuda Women’s University, Yasuhigashi, Asaminami-ku, Hiroshima 731-0153, Japan;4. Department of Obstetrics and Gynecology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramotocho, Tokushima 770-8503, Japan;1. Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;2. Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;3. Department of Pharmacology, Faculty of Medicine, University of Toronto, ON, Canada;1. Department of Agrobiological Science, Faculty of Agriculture, Ehime University, Matsuyama 790-8566, Japan;2. Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Toon 791-0212, Ehime, Japan;3. Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, 24061, Blacksburg, VA, United States;1. Department of Neurobiology, Physiology and Behavior, University of California, Davis, CA, USA;2. UFR d’odontologie, University Paris Diderot, Paris, France;3. Department of Food Science and Technology, The Ohio State University, Columbus, OH, USA |
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| Abstract: | We found that prostaglandin (PG) D2, the most abundant PG produced in the central nervous system (CNS), exhibited anxiolytic-like activity at a dose of 10–100 pmol/mouse after intracerebroventricular (i.c.v.) administration in the elevated plus-maze test in mice. A DP1 receptor-selective agonist, BW245C, mimicked the anxiolytic-like activity of PGD2, while a DP2 receptor agonist 13,14-dihydro-15-keto-PGD2 was inactive. The anxiolytic-like activity of PGD2 was blocked by a DP1 antagonist, BWA868C, suggesting that PGD2-induced anxiolytic-like activity was mediated by the DP1 receptor. Adenosine A2A or GABAA receptor antagonists, SCH58261 or bicuculline, respectively, also blocked its anxiolytic-like activity. Taken together, centrally administered PGD2 may induce anxiolytic-like activity via the A2A and GABAA receptors, downstream of the DP1 receptor. |
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