Functional antagonism of D-1 and D-2 dopaminergic mechanisms affecting striatal acetylcholine release |
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| Authors: | J M Gorell B Czarnecki S Hubbell |
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| Institution: | 1. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil;2. Department of Psychology, Universidade Braz Cubas (UBC), Mogi das Cruzes, Brazil;3. Sports Department, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil;4. Exercise and Immunometabolism Research Group, Department of Physiology and Education, Universidade do Estado de São Paulo (UNESP), Presidente Prudente, Brazil;5. Department of Biosciences, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil;6. Program of Physiology and Biophysics, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile;7. Gerencia Gestión del Conocimiento, Mutual de Seguridad, CChC, Santiago, Chile;8. Department of Physiology and Immunology, University of Barcelona, Barcelona, Spain;1. Department of Molecular Discovery Technologies, Bristol-Myers Squibb, Princeton, NJ 08543, USA;2. Department of Discovery Biology, Bristol-Myers Squibb, Princeton, NJ 08543, USA;3. Domantis, 315 Cambridge Science Park, Cambridge CB4 0WG, UK;1. Department of Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA 90089, USA;2. Graduate Aerospace Laboratories, California Institute of Technology, Pasadena, CA 91125, USA;3. Department of Mechanical Engineering, California Institute of Technology, Pasadena, CA 91125, USA;4. Department of Mechanical Engineering and Materials Science, Yale University, New Haven, CT 06511, USA |
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| Abstract: | Rat striatal slices prelabelled with 3H]choline were superfused with dopamine D-1 and D-2 agonists and antagonists, separately and in combination, during measurement of 3H]acetylcholine (ACh) release. SKF38393 (D-1 agonist), 10(-7)-10(-4) M, and SCH23390 (D-1 antagonist), 10(-7)-10(-5) M, produced a dose-dependent increase in 3H]ACh release when given separately. The increased 3H]ACh release induced by either drug could not be attenuated by sufficient L-sulpiride to block D-2 receptors. Yet both SKF38393, 10(-6)-10(-5) M, and SCH23390, 10(-6)-10(-5) M, were able to partially or fully overcome the 3H]ACh release-depressant effect of cosuperfused LY171555 (D-2 agonist), 10(-6) M. This suggests that a functional antagonism regarding striatal ACh release exists between D-1 and D-2 dopaminergic receptor-mediated mechanisms, but that D-1 modulation of local ACh release does not occur at the level of the recognition site of the striatal D-2 receptor. Finally, although attenuation of the increased release of striatal 3H]ACh induced by 10(-5) M SCH23390 by SKF38393 was seen, it is possible that such functional antagonism is not mediated by exclusively D-1 dopaminergic means. |
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