Comparison of CCK-8 receptors in the pancreas and brain of rats using CCK-8 analogues.
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概要
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The characteristics of cholecystokinin (CCK) receptors in rat pancreatic acini and in various regions of the brain were examined using synthetic CCK-8 or CCK-7 analogues. <SUP>3</SUP>H-propionylated CCK-8 ([<SUP>3</SUP>H]CCK-8) was used as a ligand. 1) The pancreatic CCK receptor had a single high affinity binding component with a dissociation constant, K<SUB>d</SUB>, of 0.76 nM and a maximum number of specific binding sites, B<SUB>maX</SUB>, of 271.91 fmol/mg protein. On the other hand, the CCK receptor in the cerebral cortex had a K<SUB>d</SUB> of 1.66 nM and a B<SUB>maX</SUB> of 30.15 fmol/mg protein. 2) The order of the potencies of CCK-7 and CCK-8 analogues with a substitution at position 3 or 4 to displace [<SUP>3</SUP>H]CCK-8 specific binding to the pancreatic acini was as follows: CCK-8>CCK-7=SucCCK-7>Suc[Sar<SUP>3</SUP>]CCK-7>Suc[D-Trp<SUP>3</SUP>]CCK-7 >Suc[D-Ala<SUP>3</SUP>]CCK-7>[D-Trp<SUP>4</SUP>]CCK-8=[D-Ala<SUP>4</SUP>]CCK-8. This order of potencies of CCK analogues was greatly different from that in the cerebral cortex. 3) The carboxy-terminal tetra-peptide (CCK-4) and penta-peptide (CCK-5) had very weak potencies in displacing [<SUP>3</SUP>H]CCK-8 binding in the pancreatic acini, which were 20 to 30-fold less than their potencies in the cerebral cortex. These results suggest that the recognition sites for CCK analogues in the pancreatic and brain CCK receptors are different.
- 公益社団法人 日本薬理学会の論文
著者
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Hoshino Minoru
Laboratory Of Bioorganic Chemistry School Of Pharmaceutical Sciences University Of Shizuoka
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Takano Yukio
Department Of Applied Physics Faculty Of Engineering University Of Tokyo
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Takeda Yasuo
Department Of Cardiac Surgery Kyusyu University School Of Medicine
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YANAIHARA NOBORU
Laboratory of Bio-Organic Chemistry, Shizuoka College of Pharmacy
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YANAIHARA CHIZUKO
Department of Bio-organic Chemistry, Shizuoka College of Pharmacy
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KAMIYA Hiro-o
Department of Pharmaceutical Sciences, Fukuoka University
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YANAIHARA Noboru
Laboratory of Cellular Metabolism, National Institute for Physiological Sciences
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ISOBE Junko
Laboratory of Cellular Metabolism, National Institute for Physiological Sciences
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SUGIURA Nobuo
Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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KASHIMOTO Kazuhisa
Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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YANAIHARA Chizuko
Department of Bioorganic Chemistry, School of Pharmaceutical Sciences, University of Shizuoka
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HOSHINO Minoru
Laboratory of Cellular Metabolism, National Institute for Physiological Sciences
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TAKEDA Yasuo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University
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