Yasuhito Ohsaka (1), Takeshi Murakami (2), Toshihide Yoshida (3) and
Yukiko Tokumitsu (1,*)
(1) Department of Physiological Chemistry, Faculty of Pharmaceutical
Sciences, Hokkaido University, Sapporo 060-0812, Japan
(2) Department of Clinical Biochemistry, Hokkaido University School of Medicine,
Sapporo 060-8638, Japan
(3) First Department of Internal Medicine, Kyoto Prefectural University
of Medicine, Kyoto 602-0841, Japan
(*) To whom correspondence should be addressed.
Abstract: 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 adipocyte. 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.
Keywords: beta3-Adrenoceptor agonist, cAMP accumulation, Free fatty acid
release, 2-Deoxyglucose uptake, beta-Adrenoceptor mRNA