Cholecystokinin - A Specific Antagonism of KSG - 504 to Chlecystokinin Receptor Binding and Pancreatic Secretion in Mammals

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概要

• 論文の詳細を見る

• The effects of KSG-504 ((<I>S</I>)-arginium (<I>R</I>)-4-[-<I>N</I>-(3-methoxypropyl)-<I>N</I>-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoate monohydrate), a new cholecystokinin (CCK)-receptor antagonist, on <SUP>125</SUP>I-CCK-8 binding to rat pancreatic, canine gallbladder and guinea pig cerebrocortical membranes and the pancreatic amylase release from isolated rat acini stimulated by several kinds of secretagogues, including CCK, were investigated. The <SUP>125</SUP>I-CCK-8 saturation experiment showed that pancreatic, gallbladder and cerebrocortical CCK receptors had a single high affinity binding component with dissociation constants (K<SUB>d</SUB>) of 0.18, 0.31 and 0.88 nM, respectively. The maximum numbers of specific binding sites (B<SUB>max</SUB>) in these membranes were 1012, 52 and 20 fmol/mg protein, respectively. KSG-504 and CCK-8 displaced specific 125I-CCK-8 binding to CCK receptors in all membrane preparations in a competitive manner. The affinity of KSG-504 for pancreatic (K<SUB>i</SUB>=173 nM) and gallbladder (K<SUB>i</SUB>=283 nM) CCK receptors were > 3 orders of magnitude higher than its affinity for cerebrocortical CCK receptors. KSG-504 also inhibited <SUP>125</SUP>I-gastrin-I binding to guinea pig gastric glands, but the IC<SUB>50</SUB> value (18.2 μM) was apparently much higher. CCK-8-stimulated amylase release from isolated pancreatic acini of rats was antagonized by KSG-504 in a concen-tration-dependent manner. KSG-504 did not affect amylase release stimulated by secretagogues such as gastrin-releasing peptide, carbachol, vasoactive intestinal peptide and A23187. These results indicate that KSG-504 acts as a CCK-A-receptor-specific antagonist in the pancreas and gallbladder.

• 社団法人 日本薬理学会の論文
• 1995-12-01

著者

• Yamazaki Yoshinobu

  Division Of Discovery Research Central Research Laboratory Kissei Pharmaceutical Co. Ltd

• Yamazaki Yoshinobu

  Central Research Laboratory Kissei Pharmaceutical Co. Ltd.

• TAKEDA Hiroo

  Division of Discovery Research, Central Research Laboratory, Kissei Pharmaceutical Co., Ltd

• AKAHANE Masuo

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.,

• KOBAYASHI Mamoru

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.,

• TAKEDA Hiroo

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.,

• AJISAWA Yukiyoshi

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.,

• SHINAGAWA Kazuhiko

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.

• Takeda Hiroo

  Division Of Discovery Research Central Research Laboratory Kissei Pharmaceutical Co. Ltd

• Akahane M

  Kissei Pharmaceutical Co. Ltd. Nagano Jpn

• Ajisawa Yukiyoshi

  Central Research Laboratories Kissei Pharmaceutical Co. Ltd.

• Shinagawa Kazuhiko

  Central Research Laboratories Kissei Pharmaceutical Co. Ltd.

• Kobayashi Mamoru

  Central Research Laboratories Kissei Pharmaceutical Co. Ltd.

• AKAHANE Masuo

  Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.

関連論文

• Pharmacological Profile of KUL-7211, a Selective β-Adrenoceptor Agonist, in Isolated Ureteral Smooth Muscle
• Characterization of β-Adrenoceptor Subtype in Bladder Smooth Muscle in Cynomolgus Monkey
• Effects of KSG-504, a New Cholecystokinin-A-Receptor Antagonist, on Pancreatic Exocrine and Endocrine Secretions in Rats
• Cholecystokinin - A Specific Antagonism of KSG - 504 to Chlecystokinin Receptor Binding and Pancreatic Secretion in Mammals
• Effects of ritodrine hydrochloride, a beta2-adrenoceptor stimulant, on uterine motilities in late pregnancy.

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