Reduction of a disulfide bond as the mechanism of action of adrenergic agonists

Various β-adrenergic agonists and antagonists were evaluated for their ability to reduce the disulfide bond in Dithionitrobenzene (DTNB), by monitoring absorbance at 412 nm, to measure reduced DTNB. In the presence of a fixed concentration of FeCl₃ (10 μM), β-adrenergic agonists, but not antagonists caused a concentration-dependent reduction of DTNB. At a concentration of 20 μM, isoproterenol, epinephrine, dopamine, norepinephrine and metaproterenol produced reduction of 0.66, 0.58, 0.44, 0.27 and 0.10 μM DTNB respectively. The β-adrenergic antagonists propranolol and dichloroisoproterenol had no effect. We suggest that β-adrenergic agonists act in association with Fe³⁺ to reduce a disulfide bond in either the receptor or a protein associated with the receptor to cause a conformational change in the protein to transmit the agonist signal to activate adenylate cyclase.