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Effect of morphine administration on rat liver metallothionein and zinc metabolism
J Hidalgo1, M Giralt, J S Garvey
1Departamento de Biología Celular y Fisiología, Facultad de Ciencias, Universidad Autónoma de Barcelona, Bellaterra, Spain.
Abstract:
The putative involvement of opioid receptors in rat liver metallothionein (MT) regulation has been studied by means of morphine administration. Rat liver MT levels were significantly increased by morphine (10 mg kg-1). This increase was blocked by the opiate antagonist naloxone (4 mg kg-1), suggesting that the effect of morphine on liver MT could involve opioid receptors. The effect of morphine appears to be mediated, at least in part, by glucocorticoids and catecholamines, inasmuch as the administration of specific receptor blockers, RU 486 (100 mg kg-1) for glucocorticoids and labetalol (5 mg kg-1) for catecholamines, diminished liver MT increase induced by morphine. These results identify a potential mediation mechanism for regulating liver MT levels. The putative role of endogenous opioids on liver MT response to stress was also studied by means of opioid receptor blockers. The effect of stress on liver MT levels was not altered by blockade of opioid receptors with either naloxone (4 mg kg-1) or naltrexone (4 mg kg-1) or diprenorphine (4 and 20 mg kg-1), suggesting that endogenous opioids are not involved in MT response to stress. Zn metabolism was also altered by morphine, as morphine administration increased liver cytosolic Zn and decreased serum Zn levels. In contrast to those found in liver MT, these changes were not naloxone-sensitive. The results obtained with RU 486 and labetalol suggest that the effect of morphine on Zn metabolism was mediated in part by glucocorticoids and catecholamines.
Insights
Morphine increases rat liver metallothionein (MT) levels, an effect blocked by naloxone, indicating opioid receptor involvement. This response is partly mediated by glucocorticoids and catecholamines, but endogenous opioids do not affect MT levels during stress.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Metallothionein (MT) is a crucial protein involved in heavy metal detoxification and cellular defense.
- Opioid receptors are known to play roles in various physiological processes, but their involvement in MT regulation is not fully understood.
Purpose of the Study:
- To investigate the role of opioid receptors in the regulation of rat liver metallothionein (MT).
- To explore the potential mediation mechanisms, including glucocorticoids and catecholamines, in morphine-induced MT changes.
- To determine the involvement of endogenous opioids in the MT response to stress.
Main Methods:
- Administration of morphine to rats to assess its effect on liver MT levels.
- Use of opioid receptor antagonists (naloxone, naltrexone, diprenorphine) to block opioid receptor activity.
- Administration of receptor blockers for glucocorticoids (RU 486) and catecholamines (labetalol) to investigate mediation pathways.
- Measurement of liver cytosolic and serum zinc (Zn) levels to assess effects on Zn metabolism.
Main Results:
- Morphine administration significantly increased rat liver MT levels.
- The morphine-induced increase in MT was blocked by the opioid antagonist naloxone.
- Glucocorticoids and catecholamines partially mediated the effect of morphine on liver MT.
- Stress-induced changes in liver MT levels were not affected by opioid receptor blockade.
- Morphine altered Zn metabolism by increasing liver cytosolic Zn and decreasing serum Zn, but these changes were not naloxone-sensitive.
Conclusions:
- Opioid receptors are involved in the regulation of rat liver metallothionein (MT) levels.
- Glucocorticoids and catecholamines play a partial role in mediating the effects of morphine on liver MT.
- Endogenous opioids are not implicated in the MT response to stress.
- Morphine affects Zn metabolism through pathways partially mediated by glucocorticoids and catecholamines, independent of opioid receptors.