The degradation of dynorphin A in brain tissue in vivo and in vitro |
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| Authors: | E A Young J M Walker R Houghten H Akil |
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| Institution: | 1. Mental Health Research Institute, University of Michigan 205 Washtenaw Place, Ann Arbor, MI 48109 USA;2. Scripps Clinic and Research Institute, Department of Immunopathology 10666 N. Torrey Pines Rd., La Jolla, CA 92036 USA;3. Department of Psychology, Brown University, Providence, RI 02912 USA;1. Department of Thyroid & Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China;2. Department of Reproductive Health Center, Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China;1. Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran;2. Institute of Biotechnology, Shiraz University, Shiraz, Iran;1. Aurigene Discovery Technologies Limited, 39-40 KIADB Industrial Area, Electronic City Phase II, Bangalore 560 100, India;2. Orion Corporation, Orionintie 1, FIN-02101 Espoo, Finland;3. Orion Corporation, Tengströminkatu 8, FIN-20101 Turku, Finland;1. Centro de Pesquisas em Biologia Molecular e Funcional (CPBMF) and Instituto Nacional de Ciência e Tecnologia em Tuberculose (INCT-TB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil;2. Programa de Pós-Graduação em Medicina e Ciências da Saúde, PUCRS, Porto Alegre, Brazil;3. Programa de Pós-Graduação em Biologia Celular e Molecular, PUCRS, Porto Alegre, Brazil;4. Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, Brazil;5. Instituto de Toxicologia e Farmacologia, PUCRS, Porto Alegre, Brazil;1. Program on Regulation, Therapeutics, and Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women''s Hospital and Harvard Medical School, Boston, MA;2. Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, MA;1. Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy;2. Department of Biomedical, Metabolic and Neural Sciences, Center for Neuroscience and Neurotechnology, University of Modena and Reggio Emilia, Modena, Italy |
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| Abstract: | The demonstration of analgesia following in vivo administration of dynorphin A (Dyn A) has been difficult. In contrast, a number of electrophysiological and behavioral effects reported with in vivo injection of Dyn A can be produced by des-tyrosine dynorphin A (Dyn A 2-17). This suggested the extremely rapid amino terminal degradation of dynorphin A. To test this hypothesis, we examined the degradation of dynorphin A following in vivo injection into the periaqueductal gray (PAG) as well as in vitro using rat brain membranes under receptor binding conditions. In vivo, we observed the rapid amino terminal cleavage of tyrosine to yield the relatively more stable destyrosine dynorphin A. This same cleavage after tyrosine was observed in vitro. Inhibition of this aminopeptidase activity in vitro was observed by the addition of dynorphin A 2-17 or dynorphin A 7-17 but not after the addition of dynorphin A 1-13, dynorphin A 1-8, dynorphin B or alpha-neo-endorphin suggesting a specific enzyme may be responsible. The detection of the behaviorally active des-tyrosine dynorphin A following in vivo injection of dynorphin A suggests that this peptide may play an important physiological role. |
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