Role of beta3-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 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.
Russell
S T
ST
Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, UK.
Hirai
K
K
Tisdale
M J
MJ
D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004822:Epididymis / Q000166:cytology; D006801:Humans; D008053:Lipid Mobilization / Q000502:physiology*; D008066:Lipolysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000652:urine; D010455:Peptides / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000502:physiology*; D015431:Weight Loss / Q000502:physiology*
D001067:Appetite Depressants; D010455:Peptides; D022702:Receptors, Adrenergic, beta-3; C008287:lipid mobilizing substance; D011433:Propranolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases