title: Sulfation of ractopamine and salbutamol by the human cytosolic sulfotransferases.
abstract: Feed additives such as ractopamine and salbutamol are pharmacologically active compounds, acting primarily as β-adrenergic agonists. This study was designed to investigate whether the sulfation of ractopamine and salbutamol may occur under the metabolic conditions and to identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating two major feed additive compounds, ractopamine and salbutamol. A metabolic labelling study showed the generation and release of [(35)S]sulfated ractopamine and salbutamol by HepG2 human hepatoma cells labelled with [(35)S]sulfate in the presence of these two compounds. A systematic analysis using 11 purified human SULTs revealed SULT1A3 as the major SULT responsible for the sulfation of ractopamine and salbutamol. The pH dependence and kinetic parameters were analyzed. Moreover, the inhibitory effects of ractopamine and salbutamol on SULT1A3-mediated dopamine sulfation were investigated. Cytosol or S9 fractions of human lung, liver, kidney and small intestine were examined to verify the presence of ractopamine-/salbutamol-sulfating activity in vivo. Of the four human organs, the small intestine displayed the highest activity towards both compounds. Collectively, these results imply that the sulfation mediated by SULT1A3 may play an important role in the metabolism and detoxification of ractopamine and salbutamol.
authors: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, OH 43614, USA.
authors: Kyounga
authors: K
authors: Ko
authors: Katsuhisa
authors: K
authors: Kurogi
authors: Garrett
authors: G
authors: Davidson
authors: Ming-Yih
authors: MY
authors: Liu
authors: Yoichi
authors: Y
authors: Sakakibara
authors: Masahito
authors: M
authors: Suiko
authors: Ming-Cheh
authors: MC
authors: Liu
mesh_terms: D000420:Albuterol / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007553:Isotope Labeling; D007700:Kinetics; D009928:Organ Specificity / Q000187:drug effects; D010627:Phenethylamines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013379:Substrate Specificity / Q000187:drug effects; D013431:Sulfates / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism*; D013460:Sulfur Isotopes
chemical_list: D010627:Phenethylamines; D013431:Sulfates; D013460:Sulfur Isotopes; C060897:ractopamine; D013455:Sulfur; D015238:Sulfotransferases; D000420:Albuterol; D004298:Dopamine