Reduction of a disulfide bond by beta-adrenergic agonists: evidence in support of a general "reductive activation" hypothesis for the mechanism of action of adrenergic agents.
Beta-adrenergic agonists, but not antagonists, were found to reduce the disulfide bond of 5,5'-dithiobis-2-nitrobenzoic acid (DTNB). The extent of DTNB reduction was proportional to the intrinsic activity for these agonists. The results suggest a novel mechanism for transmission of the signal when a beta-adrenergic agonist occupies its receptor. We proposed that beta-adrenergic agonists exert their effects to activate the adenylate cyclase by reducing a disulfide bond in the receptor (R) or guanyl nucleotide binding protein (G) component of the adenylate cyclase complex leading to tight binding of GTP to G and activation of G.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002712:Chlorides; D003574:Cytochrome c Group / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004228:Dithionitrobenzoic Acid / Q000378:metabolism; D005290:Ferric Compounds; D010084:Oxidation-Reduction
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002712:Chlorides; D003574:Cytochrome c Group; D004220:Disulfides; D005290:Ferric Compounds; D004228:Dithionitrobenzoic Acid; C024555:ferric chloride