RRC ID 61287
Author Kiso T, Namikawa T, Tokunaga T, Sawada K, Kakita T, Shogaki T, Ohtsubo Y.
Title 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.
Journal Biol Pharm Bull
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.
Volume 22(10)
Pages 1073-8
Published 1999-10-1
DOI 10.1248/bpb.22.1073
PMID 10549858
MeSH Acetates / pharmacology* Acetates / therapeutic use Adrenergic beta-Agonists / pharmacology* Adrenergic beta-Agonists / therapeutic use Animals Anti-Obesity Agents / pharmacology* Anti-Obesity Agents / therapeutic use Body Weight / drug effects CHO Cells Cricetinae Humans Hypoglycemic Agents / pharmacology* Hypoglycemic Agents / therapeutic use Male Mice Mice, Inbred C57BL Rats Receptors, Adrenergic, beta / drug effects Receptors, Adrenergic, beta / metabolism* Receptors, Adrenergic, beta-3 Transfection
IF 1.54
Human and Animal Cells CHO-K1(RCB0285)