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Published on: February 25, 2016
Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages
Tihomir Balog1, Ana Sarić, Sandra Sobocanec
1Division of Molecular Medicine, Rudjer Bosković Institute, Bijenicka cesta 54, Zagreb, Croatia. balog@irb.hr
Abstract:
Endomorphins are newly discovered mu-opioid receptor selective immunocompetent opioid peptides. Endomorphin 1 is predominantly distributed in brain, while endomorphin 2 is widely allocated in the spinal cord. Lately, endomorphins have been investigated as modulators of reactive oxygen and nitrogen species. Nitric oxide is short lived radical involved in various biological processes such as regulation of blood vessel contraction, inflammation, neurotransmission and apoptosis. The aim of this work was to investigate the in vivo effects of endomorphins on nitric oxide release and NOS 2 isoenzyme upregulation in mice peritoneal macrophages additionally challenged ex vivo with lipopolysaccharide. The results showed that endomorphin 1 or endomorphin 2 in vitro did not change NO release from peritoneal mouse macrophages during a 48 h incubation period. On the other hand in vivo endomorphins had suppressive effect on NO release as well as on NOS 2 and IL-1 protein concentration. The most of suppressive effect in vivo of both endomorphins was blocked with 30 min pretreatment with mu-receptor selective antagonist beta-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.
Insights
Endomorphins did not affect nitric oxide (NO) release in vitro but suppressed NO release, NOS 2, and IL-1 in vivo. This effect was blocked by a mu-opioid receptor antagonist, indicating opioid pathway involvement.
Area of Science:
- Immunopharmacology
- Neuroimmunology
- Opioid peptide research
Background:
- Endomorphins are novel mu-opioid receptor selective peptides.
- They have been explored as modulators of reactive oxygen and nitrogen species.
- Nitric oxide (NO) is a critical radical in biological processes, including inflammation and neurotransmission.
Purpose of the Study:
- To investigate the in vivo effects of endomorphins on nitric oxide release.
- To examine the impact of endomorphins on NOS 2 isoenzyme upregulation in mice peritoneal macrophages.
- To determine the role of the opioid receptor pathway in these effects.
Main Methods:
- Mice peritoneal macrophages were challenged ex vivo with lipopolysaccharide.
- In vitro and in vivo experiments assessed NO release and NOS 2 and IL-1 protein concentrations.
- The effect of a mu-receptor selective antagonist (beta-FNA) was evaluated.
Main Results:
- Endomorphin 1 and 2 did not alter NO release from macrophages in vitro.
- In vivo, endomorphins significantly suppressed NO release, NOS 2, and IL-1 protein levels.
- Pretreatment with the mu-receptor antagonist beta-FNA blocked the suppressive effects of endomorphins.
Conclusions:
- Endomorphins exert suppressive effects on nitric oxide production and related inflammatory markers in vivo.
- These effects are mediated through the mu-opioid receptor pathway.
- Endomorphins show potential as immunomodulators in vivo.
