Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10(-7) 10(-5) M) of the specific beta3-adrenoceptor antagonist SR59230A, Lipid mobilizing factor (250 nm) produced comparable increases in intracellular cyclic AMP in CHOKI cells transfected with the human beta3-adrenoceptor to that obtained with isoprenaline (I nm). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a beta3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the beta3-adrenoceptor showed a high affinity binding site with a Kd value 78+/-45 nm and a B-max value (282 +/- 1 fmole mg protein(-1)) comparable with that of other beta3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a beta3-adrenoceptor.