β- Adrenoceptors activate hepatic glutathione efflux through an unreported pathway

• Published in: Archives of biochemistry and biophysics 2018-04, Vol.644, p.47-56
• Main Authors: Matuz-Mares, Deyamira, Hernández-Vázquez, Alain, Riveros-Rosas, Héctor, Guinzberg, Raquel, Quesada-López, Tania, Cárabez-Trejo, Alfonso, Mora, Ofelia, Piña, Enrique
• Format: Article
• Language: English
• Subjects: Adrenaline; Calcium; CFTR; CFTRinh-172; Isoproterenol; Phenylephrine
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2018.02.018

The physiological regulation of hepatic glutathione efflux by catecholamines is poorly understood. The purpose of this work was to review the role of adrenergic receptors (AR) on total glutathione (GT) efflux in rat liver. Two models were used: isolated hepatocytes and perfused livers. In hepatocytes 10 μM adrenaline (Adr), but not isoproterenol (Iso) a β-AR agonist, or phenylephrine (Phe) an α1-AR agonist, (in a Krebs-Henseleit buffer (KHB) enriched with Ca2+ and some aminoacids) increased in 13% GT efflux. In livers perfused with KHB, Adr or Iso at 1 μmolar doses (but not Phe) stimulated 11-fold initial velocity of GT release, but only during the first 2 min of perfusion. This immediate response progressively disappeared during the following 15 min of perfusion. A second phase of GT efflux, observed between 2 and 14 min of perfusion, mimics the one reported earlier in isolated hepatocytes. The ED50 for Adr and Iso activation are in the range of 320 nM and 10 nM, respectively. Iso-mediated GT release requires Ca2+ to work, and was prevented by H89, glibenclamide, cystic fibrosis transmembrane regulator (CFTR) antibodies, and a direct CFTR inhibitor. This short-lived GT release system is associated to PKA activation and probably operates through CFTR. •A new glutathione (GSH) release system in hepatocytes is reported.•This new release system shows a huge response to Ca2+ and β-adrenergic agonists.•This response needs PKA activation to stimulate a CFTR-sensitive transporter.•This release system transiently shoots huge GSH amounts to the extracellular medium.