Beta 3-adrenergic receptor-mediated lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.
Primary adipocytes were isolated from axillary brown adipose tissue from adult cynomolgus monkeys. That this tissue contained brown adipocytes was verified by morphological examination and by demonstrating the presence of uncoupling protein messenger ribonucleic acid in the isolated adipocytes. The contributions of beta 1-, beta 2-, and beta 3-adrenergic receptors (AR) to lipolysis and oxygen consumption of isolated brown adipocytes were determined after agonist stimulation. Dose responses were determined using isoproterenol (a nonselective beta-AR agonist), denopamine (beta 1-AR agonist), procaterol (beta 2-AR agonist), and CGP12177A (beta 1- and beta 2-AR antagonist, beta 3-AR agonist). Isoproterenol, denopamine, and procaterol stimulated lipolysis with EC50 values of 4,500, and 83 nmol/L, respectively. Intrinsic activities (relative to isoproterenol maxima) were 100%, 74%, and 59%, respectively. The presence of beta 3-ARs coupled to lipolysis was demonstrated by the activity of CGP12177A (EC50 = 1.6 mumol/L; intrinsic activity = 62%). Isoproterenol stimulated oxygen consumption of brown adipocytes by 75-100% above the basal rate, with an EC50 of 1 mumol/L. Denopamine, procaterol, and CGP12177A stimulated oxygen consumption at a concentration of 100 mumol/L. These results demonstrate that all three beta-adrenergic receptor subtypes are coupled to lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.
Meyers
D S
DS
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
Skwish
S
S
Dickinson
K E
KE
Kienzle
B
B
Arbeeny
C M
CM
D000005:Abdomen; D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001365:Axilla; D001483:Base Sequence; D002046:Bupranolol / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics; D005260:Female; D007473:Ion Channels; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008252:Macaca fascicularis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D000071256:Uncoupling Protein 1
D000319:Adrenergic beta-Antagonists; D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011943:Receptors, Adrenergic, beta; D000071256:Uncoupling Protein 1; D002046:Bupranolol