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J Biol Chem, Vol. 274, Issue 53, 37770-37780, December 31, 1999
From the Wenner-Gren Institute, The Arrhenius Laboratories F3,
Stockholm University, S-106 91 Stockholm, Sweden
The mechanism behind the distinctive
non-Michaelis-Menten, bell-shaped kinetics of cAMP accumulation in
brown adipocytes (which underlies the similar kinetics of UCP1 and
A Dual Component Analysis Explains the Distinctive Kinetics of
cAMP Accumulation in Brown Adipocytes*
,
1-adrenoreceptor gene expression) was
investigated. A theoretical dual component analysis indicated that the
observed dose-response curves could be constructed as the resultant of
a stimulatory and an inhibitory component. Experimentally, inhibition
of the 
1-component of the norepinephrine response
revealed the underlying existence of a much larger stimulatory 3-component which displayed monophasic Michaelis-Menten
kinetics. The inhibitory 1-component (which was also
monophasic but had a 2-fold higher EC50) was mediated via
an increase in [Ca2+]i; the protein kinase C
pathway was not involved. The [Ca2+]i increase
which resulted in massive inhibition of cAMP accumulation was very low:
<100 nM. The [Ca2+]i signal
stimulated a calmodulin-controlled phosphodiesterase, possibly PDE-1. The acquirement of this specific
interaction pattern between - and 1-adrenergic
stimulation was thus part of the differentiation program of the brown
adipocytes. It was concluded that an array of synergistic or inhibitory
1/ interactions occur in the adrenergic regulation of
this cell type which is unique in its dependence upon adrenergic
stimulation for cellular proliferation, differentiation, and metabolic function.
*
This work was supported by a grant from the Swedish Natural
Science Research Council (to B. C. and J. N.) and Russian
Foundation for Basic Research Grant 98-04-49214 (to G. B.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
On leave from the Institute of Cell Biophysics, Russian Academy of
Sciences, Pushchino, Russia. Present address: Centre for Molecular
Biology and Medicine, Epworth Hospital, 89 Bridge Rd., Richmond
(Melbourne), 3121 Australia.
§
To whom correspondence should be addressed: The Wenner-Gren
Institute, The Arrhenius Laboratories F3, Stockholm University, S-106
91 Stockholm, Sweden. Tel.: 46-8-164128; Fax: 46-8-156756; E-mail:
jan@metabol.su.se.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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