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Opioids inhibit the induction of nitric oxide synthase in J774 macrophages
T Iuvone1, A Capasso, F D'Acquisto
1Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Abstract:
The effect of opioids on NO production by LPS-stimulated murine macrophages J774 has been investigated. Morphine (mu and k opioid receptor agonist), DAGO (selective mu receptor agonist) and U50-488H (selective k receptor agonist), added (10(-10)-10(-6) M) to the cells 0.5 h before activation with LPS, significantly inhibited NO production. This effect was reverted by naloxone (10(-12)-10(-8) M), an opioid specific antagonist. In contrast, DPDPE and deltorphin II respectively delta 1 and delta 2 receptor agonists (10(-10)-10(-6) M) did not affect NO generation. Morphine was not able to inhibit NO production when added after LPS challenge. The results of the present study indicate that opioids are able to inhibit NO formation in LPS-activated macrophages through the involvement of specific opioid receptors. Moreover, the ability of morphine to inhibit NO production only when given before LPS challenge suggests that the opiate inhibits the induction but not the activity of the inducible NO synthase.
Insights
Opioids, including morphine, suppress nitric oxide (NO) production in LPS-activated macrophages by engaging specific opioid receptors. This inhibition affects NO induction, not its activity, and can be reversed by naloxone.
Area of Science:
- Immunology
- Pharmacology
- Neuroscience
Background:
- Macrophages play a crucial role in immune responses, including the production of nitric oxide (NO) upon stimulation.
- Opioid receptors are known to modulate immune cell function, but their specific effects on NO production in macrophages require further elucidation.
Purpose of the Study:
- To investigate the impact of various opioids on nitric oxide (NO) generation in lipopolysaccharide (LPS)-stimulated murine macrophages (J774 cell line).
- To determine the specific opioid receptor subtypes involved in mediating these effects.
- To ascertain whether opioids inhibit NO induction or activity.
Main Methods:
- Murine macrophage cell line J774 was treated with opioids (morphine, DAGO, U50-488H, DPDPE, deltorphin II) or vehicle prior to LPS stimulation.
- Nitric oxide (NO) production was measured.
- The effect of naloxone, an opioid antagonist, was assessed.
- The timing of opioid administration (before or after LPS) was varied.
Main Results:
- Morphine, DAGO (mu-selective), and U50-488H (kappa-selective) significantly inhibited NO production in LPS-stimulated macrophages.
- DPDPE and deltorphin II (delta-selective agonists) did not affect NO generation.
- Naloxone reversed the inhibitory effects of morphine, DAGO, and U50-488H.
- Morphine inhibited NO production only when administered before LPS, not after.
Conclusions:
- Opioids, acting through mu and kappa opioid receptors, can inhibit NO formation in activated macrophages.
- The findings suggest that opioids primarily affect the induction of inducible nitric oxide synthase (iNOS), rather than its enzymatic activity.
- These results highlight a novel immunomodulatory role for opioids via specific receptor interactions.