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β- Adrenoceptors activate hepatic glutathione efflux through an unreported pathway.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2018 Apr 15; Vol. 644, pp. 47-56. Date of Electronic Publication: 2018 Feb 26. - Publication Year :
- 2018
-
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 (G <subscript>T</subscript> ) 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 α <subscript>1</subscript> -AR agonist, (in a Krebs-Henseleit buffer (KHB) enriched with Ca <superscript>2+</superscript> and some aminoacids) increased in 13% G <subscript>T</subscript> efflux. In livers perfused with KHB, Adr or Iso at 1 μmolar doses (but not Phe) stimulated 11-fold initial velocity of G <subscript>T</subscript> 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 G <subscript>T</subscript> efflux, observed between 2 and 14 min of perfusion, mimics the one reported earlier in isolated hepatocytes. The ED <subscript>50</subscript> for Adr and Iso activation are in the range of 320 nM and 10 nM, respectively. Iso-mediated G <subscript>T</subscript> release requires Ca <superscript>2+</superscript> to work, and was prevented by H89, glibenclamide, cystic fibrosis transmembrane regulator (CFTR) antibodies, and a direct CFTR inhibitor. This short-lived G <subscript>T</subscript> release system is associated to PKA activation and probably operates through CFTR.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenergic alpha-1 Receptor Agonists pharmacology
Adrenergic beta-Agonists pharmacology
Animals
Hepatocytes cytology
Isoproterenol pharmacology
Liver cytology
Male
Phenylephrine pharmacology
Rats
Rats, Wistar
Receptors, Adrenergic, alpha-1 metabolism
Glutathione metabolism
Hepatocytes metabolism
Liver metabolism
Receptors, Adrenergic, beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 644
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 29496543
- Full Text :
- https://doi.org/10.1016/j.abb.2018.02.018