Central antisecretory and peripheral gastroprotective effects of GBR 12909, a selective dopamine uptake inhibitor |
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| Affiliation: | 1. Department of Physiology, School of Medical Sciences, Tarbiat Modares University, PO Box: 14115-331, Tehran, Iran;2. Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran;3. Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;1. College of Food Science and Engineering, Ocean University of China, No.5 Yushan Road, Qingdao 266003, PR China;2. Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, Shandong Province, PR China;3. Rutgers State Univ, Dept Food Sci, 65 Dudley Rd, New Brunswick, NJ 08901, USA;1. Instituto de Biología Agrícola de Mendoza (IBAM-CONICET), Facultad de Ciencias Agrarias, Universidad Nacional de Cuyo, Mendoza, Argentina;2. Instituto de Química de San Luis (INQUISAL-CONICET), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina;3. Instituto Nacional de Tecnología Agropecuaria (INTA-Bariloche), Estación Experimental Agropecuaria Bariloche, CONICET, Río Negro, Argentina;1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China;2. Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, China;3. Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, 410008, China;4. College of Life Science, Central South University, Changsha, 410078, China;5. Department of Anesthesia, The Third Xiangya Hospital of Central South University, Changsha, 410013, China;6. Department of Spine Surgery, Xiangya Hospital of Central South University, Changsha, 410008, China;7. Department of Obstetrics and Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China;8. Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China;9. College of Biology, Hunan University, Changsha, 410012, China |
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| Abstract: | A variety of dopaminergic compounds influence gastric secretion and response to injury. In particular, agonists of the D1 receptor are gastroprotective when given either centrally of peripherally. In the present studies, we show that an indirect dopamine (DA) promoter, GBR 12909, a selective DA uptake inhibitor given ip but not icv, protects against restraint-cold stress-induced gastric mucosal injury. This protection likely occurred through preservation of gastric adherent mucus, since all doses of GBR 12909 resulted in gastric mucus levels at or near control (non-stressed) values. When given, ip, GBR 12909 did not influence basal gastric acid secretion in conscious rats, however, when given icv, GBR 12909 inhibited gastric acid secretion with an ED50 of about 0.5 ug (1.13 umoles). We conclude that both central and peripheral DA contributes to gastrointestinal integrity through reduction of aggressive elements in the gut as well as by enhancing gastric mucosal defence. |
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