BETA(3)-ADRENERGIC RECEPTOR-MEDIATED LIPOLYSIS AND OXYGEN-CONSUMPTIONIN BROWN ADIPOCYTES FROM CYNOMOLGUS MONKEYS

Primary adipocytes were isolated from axillary brown adipose tissue fr om adult cynomolgus monkeys. That this tissue contained brown adipocyt es was verified by morphological examination and by demonstrating the presence of uncoupling protein messenger ribonucleic acid in the isola ted adipocytes. The contributions of beta(1)-, beta(2)-, and beta(3)-a drenergic receptors (AR) to lipolysis and oxygen consumption of isolat ed brown adipocytes were determined after agonist stimulation. Dose re sponses were determined using isoproterenol (a nonselective P-AR agoni st), 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 EC(50) values of 4,500, and 83 nmol/L, respectively. Intrinsic activi ties (relative to isoproterenol maxima) were 100%, 74%, and 59%, respe ctively. The presence of beta(3)-ARs coupled to lipolysis was demonstr ated by the activity of CGP12177A (EC(50) = 1.6 mu mol/L; intrinsic ac tivity = 62%). Isoproterenol stimulated oxygen consumption of brown ad ipocytes by 75-100% above the basal rate, with an EC(50) of 1 mu mol/L . Denopamine, procaterol, and CGP12177A stimulated oxygen consumption at a concentration of 100 mu mol/L. These results demonstrate that all three beta-adrenergic receptor subtypes are coupled to lipolysis and oxygen consumption in brown adipocytes from cynomolgus monkeys.