Role of beta3-adrenergic receptors in the action of a tumour lipid mobilizing factor.

Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, UK.

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 CHOK1 cells transfected with the human beta3-adrenoceptor to that obtained with isoprenaline (1 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. Copyright 2002 The Cancer Research Campaign

PMID: 11875710 [PubMed - indexed for MEDLINE]