Comparison of atypical beta3-adrenoceptor agonists with their respective metabolic activities in rat white adipocytes.
The metabolic activities of four types of beta3-adrenoceptor (AR) agonists, BRL35135A, BRL28410, ICI215001 and CL316243, were compared with those of other beta1- and beta2-AR agonists in rat white adipocytes. All the beta3-AR agonists caused cAMP formation, free fatty acid release and 2-deoxyglucose uptake; the maximum activity levels were similar except for ICI215001, which was lower. However, the magnitude of potency and selectivity of these agonists differed. The most potent and selective beta3-agonist was CL316243. Metabolic activities and Northern blotting showed that there were three beta-AR subtypes that were coupled to adenylyl cyclase and contributed to the induction of lipolysis and glucose uptake. The rank order of the amounts of beta-AR subtypes was beta3 >>beta1> beta2. However, the physiological functions of beta-AR subtypes were essentially similar in rat white adipocytes. On the other hand, cAMP accumulation and Northern blotting showed that human adipocytes predominantly contained beta2-AR, with far lower levels of beta1- and beta3-ARs. These findings suggested that the beta3-AR plays an important role in energy metabolism and thermogenesis in which cross talk exists between beta1- and beta3-ARs in rat adipocytes, while beta2-AR is the most important for the lipolysis regulation in human subcutaneous adipocytes.
Ohsaka
Y
Y
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Murakami
T
T
Yoshida
T
T
Tokumitsu
Y
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D003847:Deoxyglucose / Q000378:metabolism; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000235:genetics; D022702:Receptors, Adrenergic, beta-3
D000318:Adrenergic beta-Agonists; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D003847:Deoxyglucose; D000242:Cyclic AMP; D000262:Adenylyl Cyclases