Examination of the role of catecholamines in hepatic glutathione suppression by cold-restraint in mice

Toxicology. 1991 Mar 25;67(1):29-40. doi: 10.1016/0300-483x(91)90161-s.


Cold-restraint stress was found to produce a depression in hepatic glutathione content and to elevate circulating catecholamine levels in four mouse strains--ICR, NIH, B6C3F1, and ND/4. Serum norepinephrine concentrations were significantly elevated after cold-restraint (2--3 h) in all strains, and serum epinephrine levels were increased in the B6C3F1 and ND/4 strains. In time-course studies conducted using ND/4 mice, the decline in hepatic glutathione concentrations was found to slightly precede increases in serum epinephrine and norepinephrine concentrations. Also, pretreatment with phentolamine, an alpha-adrenoreceptor antagonist compound shown in previous studies to block epinephrine-induced hepatic glutathione suppression, had no effect on glutathione losses from cold-restraint. These observations are inconsistent with catecholamines as sole mediators of cold-restraint induced hepatic glutathione depression. Two other endogenous substances elevated during stress, corticosteroids and glucagon, were found to diminish glutathione concentrations in the liver in ND/4 mice when administered exogenously. The effects of catecholamines (epinephrine), corticosteroids (hydrocortisone) and glucagon were not additive, i.e. the depression in glutathione when these agents were administered in combination was generally no greater than that induced when the most effective agent was administered alone. It is postulated that during cold-restraint stress multiple endogenous agents are released which are independently capable of causing a depression in hepatic glutathione content.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Temperature
  • Catecholamines / blood
  • Catecholamines / metabolism*
  • Cold Temperature / adverse effects*
  • Epinephrine / blood
  • Epinephrine / metabolism
  • Epinephrine / pharmacology
  • Glucagon / pharmacology
  • Glutathione / metabolism*
  • Hydrocortisone / pharmacology
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mice, Inbred Strains
  • Norepinephrine / blood
  • Norepinephrine / metabolism
  • Phentolamine / pharmacology
  • Propranolol / pharmacology
  • Stress, Physiological / metabolism*


  • Catecholamines
  • Glucagon
  • Propranolol
  • Glutathione
  • Hydrocortisone
  • Norepinephrine
  • Epinephrine
  • Phentolamine