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The BB2 receptor antagonist BW2258U89 attenuates the feeding responses evoked by exogenous gastrin releasing peptide-29
Affiliation:1. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan;2. Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan;3. Department of Pharmacology, Fudan University Shanghai Medical College, 138 Yixueyuan Road, Shanghai 200032, China;1. Vascular Biotechnology Laboratory, Baker IDI, Melbourne, Australia;2. Atherothrombosis and Vascular Biology Laboratory, Baker IDI, Melbourne, Australia;3. Departments of Nuclear Medicine and Centre for PET, Austin Hospital, Melbourne, Australia;4. Department of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia;5. Ludwig Institute for Cancer Research, Austin Hospital, Melbourne, Australia;6. The Florey Institute of Neuroscience and Mental Health, Austin Hospital, Melbourne, Australia;7. Central Clinical School, Monash University, Melbourne, Australia;1. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan;2. Mushroom Research Laboratory, Hokuto Corporation, 800-8, Shimokomazawa, Nagano, 381-0008, Japan;3. Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan;4. Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Miyagi, 980-8574, Japan;5. Department of Pharmacy, Yamagata University Hospital, Yamagata, 990-9585, Japan
Abstract:This confirmatory work is aimed to test that the hypothesis that the gastrin releasing peptide (GRP) receptor – the BB2 receptor – is necessary for reduction of meal size (MS) and prolongation of the intermeal interval (IMI) by the small and the large forms of GRP in the rat, GRP-10 and GRP-29, and to confirm the sites of action regulating such responses – the vascular bed of the celiac artery (CA, supplying stomach and upper duodenum). To pursue these aims we measured first MS and IMI length in response to GRP-10 and GRP-29 (0, 0.5 nmol/kg) infused in the CA (n = 8 rats) and the cranial mesenteric artery (CMA, supplying the small and part of the large intestine, n = 8 rats) in near spontaneously free feeding rats pretreated with the BB2 receptor antagonist BW2258U89 (0.1 mg/kg) in the same arteries prior to the onset of the dark cycle. We found that GRP-29, but not GRP-10, infused by the CA reduced MS and prolonged the IMI by decreasing meal latency and meal duration and the BB2 receptor antagonist BW2258U89 infused in the same artery attenuated these responses. These results suggest that the BB2 receptor is necessary for reduction of MS and prolongation of the IMI by exogenous GRP-29, and the vascular bed of the CA, stomach and upper duodenum, contains sites of action regulating these feeding responses.
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