[Adenylate cyclase response to beta-adrenergic agonists in heart and brown adipose tissue].
Some sympathomimetic compounds (i.e. BRL37344) increase brown adipose tissue (BAT) thermogenesis with minimal cardiac effects. They act through an "atypical" beta-adrenergic receptor (beta-AR). Since beta-AR responses involve Adenylate Cyclase (AC) activation, we investigate the AC answer to isoproterenol and BRL37344 in rat plasmamembranes of heart (beta 1-ARs) and BAT (atypical beta-ARs). AC dose-response curves were obtained by incubating membrane fractions with different concentrations of isoproterenol and BRL37344 (1 nM-100 microM) at 25 degrees C for 15 min. In our study BRL37344 is 40-times more potent than isoproterenol in stimulating AC activity of BAT (EC50s: BRL37344 = 0.02 microM, isoproterenol = 0.7 microM). Furthermore it is more potent in stimulating BAT AC than heart AC (BRL37344 EC50 ratio heart/BAT = 38). However on BAT membranes, BRL37344 intrinsic sympathomimetic activity (ISA) vs. Isoproterenol is 0.87. Since isoproterenol and BRL37344 show a similar ISA for BAT respiration and lipolysis, we may argue that AC maximal activity is not required for maximal lipolytic and thermogenic responses.
Garruti
G
G
Clinica Medica III, Università di Bari.
De Pergola
G
G
Cignarelli
M
M
Stock
M
M
Giorgino
R
R
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; C057368:BRL 37344; D000262:Adenylyl Cyclases; D007545:Isoproterenol