Norepinephrine utilizes alpha 1- and beta-adrenoreceptors synergistically to maximally induce c-fos expression in brown adipocytes. 1994

H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, Sweden.

In order to examine how norepinephrine stimulates proliferation and differentiation in brown fat cells, we have investigated the ability of brown fat cells to respond to norepinephrine stimulation with an increase in the expression of the proto-oncogene c-fos. Stimulation of brown fat precursor cells (isolated from young mice and grown for 4 days in culture) with norepinephrine led to a marked but transient (maximal approximately 30 min) induction of c-fos expression. The magnitude of this induction was similar in pre- and postconfluent cells. The norepinephrine effect could be blocked by both alpha 1- and beta-adrenergic antagonists. Forskolin had a small inductive ability, as had the selective alpha 1-agonist cirazoline, but with both together a high induction was obtained. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) could in itself induce c-fos expression, but pretreatment with TPA did not abolish the ability of norepinephrine to induce c-fos expression, indicating that TPA-sensitive protein kinase C was not a primary mediator in this pathway. Also the Ca2+ ionophore A23187 had in itself an inductive ability, but A23187 in combination with forskolin led to a large increase in c-fos expression, indicating synergistic interaction between a cAMP pathway and a [Ca2+]i pathway. This interaction was not proximal, i.e. alpha 1 stimulation or increase in [Ca2+]i by A23187 did not augment forskolin-induced cAMP levels, and beta stimulation or forskolin did not affect [Ca2+]i levels; and it did not require protein synthesis. It was concluded that norepinephrine, in agreement with its fundamental role in the control of brown fat cell growth and development, was able to induce c-fos expression, that this induction was not exclusively linked to promotion of either proliferation or differentiation, and that the induction was mediated via a distal synergism between beta/cAMP and alpha 1/[Ca2+]i pathways, thus conferring to the alpha 1-adrenoreceptors on the cell a potentially significant role in the control of cell growth and development.

UI MeSH Term Description Entries
D008297 Male Males
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011943 Receptors, Adrenergic, beta One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS. Adrenergic beta-Receptor,Adrenergic beta-Receptors,Receptors, beta-Adrenergic,beta Adrenergic Receptor,beta-Adrenergic Receptor,beta-Adrenergic Receptors,Receptor, Adrenergic, beta,Adrenergic Receptor, beta,Adrenergic beta Receptor,Adrenergic beta Receptors,Receptor, beta Adrenergic,Receptor, beta-Adrenergic,Receptors, beta Adrenergic,beta Adrenergic Receptors,beta-Receptor, Adrenergic,beta-Receptors, Adrenergic
D002001 Adipose Tissue, Brown A thermogenic form of adipose tissue composed of BROWN ADIPOCYTES. It is found in newborns of many species including humans, and in hibernating mammals. Brown fat is richly vascularized, innervated, and densely packed with MITOCHONDRIA which can generate heat directly from the stored lipids. Brown Fat,Hibernating Gland,Brown Adipose Tissue,Fat, Brown,Tissue, Brown Adipose
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
November 2007, American journal of physiology. Endocrinology and metabolism,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
June 1999, The American journal of physiology,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
January 2000, BMC cell biology,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
January 1992, Archives of medical research,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
August 1989, Biochemical and biophysical research communications,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
January 1982, International journal of obesity,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
April 1985, The American journal of physiology,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
November 2005, Biochemical and biophysical research communications,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
September 1995, Canadian journal of physiology and pharmacology,
H Thonberg, and S J Zhang, and P Tvrdik, and A Jacobsson, and J Nedergaard
September 2018, Biochemical and biophysical research communications,
Copied contents to your clipboard!