Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Anti-obesity and Anti-diabetic Activities of a New β3 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-Ay Mice
Tatsuya KISOTomoko NAMIKAWATetsuhiro TOKUNAGAKazuyuki SAWADATakao KAKITATakeshi SHOGAKIYoshikazu OHTSUBO
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1999 Volume 22 Issue 10 Pages 1073-1078

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Abstract

We investigated the β-adrenergic receptor (AR) agonistic activities in rats and humans, and the anti-obesity and anti-diabetic activities in KK-Ay mice, of a new β3-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 (β1-AR activity) and white adipocyte lipolysis (β3-AR activity), but did not induce uterine muscle relaxation (β2-AR activity). The β3-AR agonistic activity of SWR-0342SA was about 20 times stronger than its β1-AR agonistic activity. Similarly, SWR-0342SA enhanced the accumulation of cAMP in Chinese hamster ovary (CHO) cells expressing human β1- and β3-ARs, while having no effect in CHO cells expressing β2-ARs. Adenylyl cyclase stimulation by SWR-0342SA in CHO cells expressing β3-ARs was about 35 times higher than that in CHO cells expressing β1-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-Ay 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-Ay mice.These results indicated that SWR-0342SA is a selective β3-AR agonist, and possesses potent anti-diabetic activity, and that the anti-obesity activity is inferior to the anti-diabetic activity.

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© The Pharmaceutical Society of Japan
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