Endothelin-3 stimulates inositol 1,4,5-trisphosphate production and Ca2+ influx to produce biphasic dopamine release from rat striatal slices |
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Authors: | Yasufumi Kataoka Shuichi Koizumi Masami Niwa Hirotomo Shibaguchi Kazuto Shigematsu Yoshihisa Kudo Kohtaro Taniyama |
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Affiliation: | (1) Department of Pharmacology 2, Nagasaki University School of Medicine, 1-12-4 Sakamoto, 852 Nagasaki, Japan;(2) Division of Pharmacology, National Institute of Health of Science, 1-18-1 Kamiyoga, Setagaya-ku, 158 Tokyo, Japan;(3) Department of Pathology 2, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki University, 852, Japan;(4) Department of Neuroscience, Mitsubishi-Kasei Institute of Life Sciences, 11 Minamiooya, Machidashi, 194 Tokyo, Japan |
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Abstract: | Summary 1. Real-time monitoring of dopamine (DA) release from rat striatal slices demonstrated that endothelin (ET)-3 (0.1–10M) produced a biphasic DA release consisting of transient and sustained components. When extracellular Ca2+ was removed, the sustained but not transient response remarkably decreased.2. ET-3 (1–10M) stimulated an increase in the intracellular Ca2+ concentration ([Ca2+]i), which also consisted of two components. The external Ca2+ depletion inhibited primarily the sustained component of the Ca2+ response to ET-3.3. ET-3 increased inositol 1,4,5-trisphosphate (IP3) concentrations in striatal slices. This response peaked at 10 to 20 sec and returned to the basal level 2 min after stimulation, an event which was in good accord with a prompt and transient phase of both cytosolic Ca2+ activity and DA release evoked by ET-3.4. Thus, ET-3 produces a transient and a sustained release of DA from striatal slices by stimulating intracellular Ca2+ mobilization via IP3 formation and extracellular Ca2+ influx, respectively. |
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Keywords: | endotheline-3 dopamine release intracellular Ca2+ concentration inositol 1,4,5-trisphosphate striatal slices |
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