Alpha 2-adrenergic stimulation promotes preadipocyte proliferation. Involvement of mitogen-activated protein kinases.
Primary cultures of rat preadipocytes were shown to express alpha 2- and beta-adrenoreceptors when maintained in serum-deprived medium. alpha 2-Adrenoreceptor stimulation led to an increase in cell number, whereas beta-adrenoreceptor stimulation was without effect. On 3T3-F442A clones stably transfected with the human alpha 2-C10 gene and expressing a physiologically related number of alpha 2-adrenoreceptors to overexpression, the proliferative effect of alpha 2-adrenoreceptor agonist UK14304 was proportional to the level of alpha 2-adrenoreceptor expressed in individual clones and required alpha-2 adrenoreceptor stimulation. Analysis of the signaling pathway linked to alpha 2-adrenoreceptor activation showed that the mitogenic effect was adenylyl cyclase- and protein kinase C-independent. It was pertussis toxin-sensitive, implying the involvement of pertussis toxin-sensitive G proteins. The activation of the mitogen-activated protein kinase pathway was increased after alpha 2-adrenoreceptor stimulation in both 3T3-F442 clones and rat preadipocytes and inhibited by pertussis toxin treatment. So, catecholamines are involved in the control of white preadipocyte proliferation through the alpha 2-adrenoreceptor activation, linked to the mitogen-activated protein kinase pathway.
Bouloumié
A
A
INSERM Unité 317, Centre Hospitalier Universitaire Rangueil, Institut L. Bugnard, Université Paul Sabatier, Toulouse, France.
Planat
V
V
Devedjian
J C
JC
Valet
P
P
Saulnier-Blache
J S
JS
Record
M
M
Lafontan
M
M
D016475:3T3 Cells; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D000068438:Brimonidine Tartrate; D003994:Bucladesine / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003000:Clonidine / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D006801:Humans; D019329:Idazoxan / Q000031:analogs & derivatives; D007700:Kinetics; D008297:Male; D051379:Mice; D037342:Pertussis Toxin; D011807:Quinolizines / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011807:Quinolizines; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C054290:L 657743; D000068438:Brimonidine Tartrate; D003994:Bucladesine; D000242:Cyclic AMP; C058525:2-methoxyidazoxan; D037342:Pertussis Toxin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D003000:Clonidine; D019329:Idazoxan