Anti-obesity and anti-diabetic activities of a new beta3 adrenergic receptor agonist, (S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-propenyl] phenoxy] acetic acid ethanedioic acid (SWR-0342SA), in KK-Ay mice.

Abstract

We investigated the beta-adrenergic receptor (AR) agonistic activities in rats and humans, and the anti-obesity and anti-diabetic activities in KK-Ay mice, of a new beta3-AR agonist, SWR-0342SA ((S)-(Z)-[4-[[1-[2-[(2-hydroxy-3-phenoxypropyl)]amino]ethyl]-1-pro penyl]phenoxy] acetic acid ethanedioic acid). With regards to its beta-AR agonistic activity in rats, SWR-0342SA stimulated the atrial beating rate (beta1-AR activity) and white adipocyte lipolysis (beta3-AR activity), but did not induce uterine muscle relaxation (beta2-AR activity). The beta3-AR agonistic activity of SWR-0342SA was about 20 times stronger than its beta1-AR agonistic activity. Similarly, SWR-0342SA enhanced the accumulation of cAMP in Chinese hamster ovary (CHO) cells expressing human beta1- and beta3-ARs, while having no effect in CHO cells expressing beta2-ARs. Adenylyl cyclase stimulation by SWR-0342SA in CHO cells expressing beta3-ARs was about 35 times higher than that in CHO cells expressing beta1-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 beta3-AR agonist, and possesses potent anti-diabetic activity, and that the anti-obesity activity is inferior to the anti-diabetic activity.

• Authors: T Kiso, T Namikawa, T Tokunaga, K Sawada, T Kakita, T Shogaki, Y Ohtsubo
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 22 Issue 10 Pg. 1073-8 (Oct 1999) ISSN: 0918-6158 [Print] Japan
• PMID: 10549858 (Publication Type: Journal Article)

Chemical References

• Acetates
• Adrenergic beta-Agonists
• Anti-Obesity Agents
• Hypoglycemic Agents
• Receptors, Adrenergic, beta
• Receptors, Adrenergic, beta-3
• SWR 0342SA

Topics

• Acetates (pharmacology, therapeutic use)
• Adrenergic beta-Agonists (pharmacology, therapeutic use)
• Animals
• Anti-Obesity Agents (pharmacology, therapeutic use)
• Body Weight (drug effects)
• CHO Cells
• Cricetinae
• Humans
• Hypoglycemic Agents (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Rats
• Receptors, Adrenergic, beta (drug effects, metabolism)
• Receptors, Adrenergic, beta-3
• Transfection