ß- Adrenoceptors activate hepatic glutathione efflux through an unreported pathway.
Arch Biochem Biophys
; 644: 47-56, 2018 04 15.
Article
em En
| MEDLINE
| ID: mdl-29496543
ABSTRACT
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⯵M adrenaline (Adr), but not isoproterenol (Iso) a ß-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 2â¯min of perfusion. This immediate response progressively disappeared during the following 15â¯min of perfusion. A second phase of GT efflux, observed between 2 and 14â¯min of perfusion, mimics the one reported earlier in isolated hepatocytes. The ED50 for Adr and Iso activation are in the range of 320â¯nM and 10â¯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.
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MEDLINE
Assunto principal:
Receptores Adrenérgicos beta
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Hepatócitos
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Glutationa
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Fígado
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article