title: Discrepancies between the affinities of binding and action of the novel beta-adrenergic agonist BRL 37344 in rat brown adipose tissue.
abstract: The novel brown adipose tissue (BAT) selective beta-adrenergic agonist, BRL 37344, is 31-fold more potent than (-)-isoproterenol in stimulating the respiratory rate of interscapular BAT fragments. BRL 37344 is also more potent (9-fold) than (-)-isoproterenol in stimulating adenylate cyclase activity of IBAT purified plasma membranes whereas, in the same preparation, it is 81-fold less potent than (-)-isoproterenol in competition displacement studies with the beta-adrenergic ligand, [125I]cyanopindolol. We have previously demonstrated that the photoaffinity reagent [125I]cyanopindolol-diazirine selectively labels a 62 kDa protein in IBAT plasma membranes that displays pharmacological properties of a beta 1-adrenergic subtype. Relatively high concentrations of BRL 37344 (10 microM) are required to displace [125I]cyanopindolol-diazirine binding to the 62 kDa protein. Taken together, the results suggest that two different populations of beta-adrenergic receptors may co-exist in BAT plasma membranes: a small population (about 15%) of atypical beta-receptors and a large population of beta 1-receptors that exhibit high and low affinities for BRL 37344, respectively.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000201:enzymology; D004983:Ethanolamines / Q000378:metabolism* / Q000494:pharmacology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012016:Reference Values
chemical_list: D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C057368:BRL 37344; D020120:Iodocyanopindolol; D010869:Pindolol; D000262:Adenylyl Cyclases; D007545:Isoproterenol