Anti-obesity and Anti-diabetic Activities of a New β_3 Adrenergic Receptor Agonist, (S)-(Z)-[4-[[1-[2-[(2-Hydroxy-3-phenoxypropyl)]amino]athyl]-1-propenyl]phenoxy] Acetic Acid Ethanedioic Acid (SWR-0342SA), in KK-A^y Mice

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概要

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• We investigated the β-adrenergic receptor (AR) agonistic activities in rats and humans, and the anti-obesity and anti-diabetic activities in KK-A^y mice, of a new β_3-AR agonist, SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl]phenoxy] acetic acid ethanedioic acid). With regards to its β-AR agonistic activity in rats, SWR-0342SA stimulated the atrial beating rate (β_1-AR activity) and white adipocyte lipolysis (β_3-AR activity), but did not induce uterine muscle relaxation (β_2-AR activity). The β_3-AR agonistic activity of SWR-0342SA was about 20 times stronger than its β_1-AR agonistic activity. Similarly, SWR-0342SA enhanced the accumulation of cAMP in Chinese hamster ovary (CHO) cells expressing human β_1- and β_3-ARs, while having no effect in CHO cells expressing β_2-ARs. Adenylyl cyclase stimulation by SWR-0342SA in CHO cells expressing β_3-ARs was about 35 times higher than that in CHO cells expressing β_1-ARs. With regards to anti-obesity and anti-diabetic activities, SWR-0342SA had no effect on body weight or food intake, but slightly decreased the fat pads weight in KK-A^y mice, an animal model of obesity and non-insulin-dependent diabetes mellitus (NIDDM). On the other hand, SWR-0342SA significantly decreased both blood glucose (to about 46% of control) and serum insulin levels (to about 40% of control) in KK-A^y mice.These results indicated that SWR-0342SA is a selective β_3-AR agonist, and possesses potent anti-diabetic activity, and that the anti-obesity activity is inferior to the anti-diabetic activity.

• 公益社団法人日本薬学会の論文
• 1999-10-15

著者

• Nagatomo T

  Dep. Of Pharmacology Fac. Of Pharmaceutical Sciences Niigata Univ. Of Pharmacy And Applied Life Scie

• Tokunaga Tatsuhiro

  Molecular Chemistry Resarch Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceut

• 正垣 武志

  Research Department Sawai Pharmaceutical Co. Ltd.

• KISO Tatsuya

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• NAMIKAWA Tomoko

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• TOKUNAGA Tetsuhiro

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• SAWADA Kazuyuki

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• KAKITA Takao

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• SHOGAKI Takeshi

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• OHTSUBO Yoshikazu

  Research Department, Sawai Pharmaceutical Co., Ltd.,

• Kiso Tatsuya

  Research Department Sawai Pharmaceutical Co. Ltd.

• Kakita T

  Research Department Sawai Pharmaceutical Co. Ltd.

• Nagatomo Takafumi

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Niigata University Of Pharmacy And App

• Tokunaga T

  Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Sawada Kazuyuki

  Research Department Sawai Pharmaceutical Co. Ltd.

• Ohtsubo Yoshikazu

  Biological Res. Dep. Sawai Pharmaceutical Co. Ltd.

• Namikawa Tomoko

  Biological Res. Dep. Sawai Pharmaceutical Co. Ltd.

• OHTSUBO Yoshikazu

  Research Department, Sawai Pharmaceutical Co. Ltd.

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