Endomorphin-suppressed nitric oxide release from mice peritoneal macrophages

Abstract 

Endomorphins are newly discovered μ-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 48h 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 30min pretreatment with μ-receptor selective antagonist β-FNA, which proved involvement of opioid receptor pathway in suppressive effects of endomorphins.

Abbreviations: β-FNA, β-funaltrexamine hydrochloride, FBS, fetal bovine serum, HBSS, Hanks’s balanced salt solution, IL-1, interleukin-1, LPS, lipopolysaccharide, NO, nitric oxide, NOS, nitric oxide synthase, PEM, peritoneal macrophages, RNS, reactive nitrogen species, ROS, reactive oxygen species, TNF, tumor necrosis factor

Keywords: Endomorphin 1, Endomorphin 2, Nitric oxide, Interleukin-1, Peritoneal macrophages