Participation of neuropeptide Y and its receptors in leukotriene formation in the pig inflamed endometrium

Uterine inflammation is a very common reproductive disorder in farm animals that can result from disturbances in endometrial immune defense mechanisms. Inflammation stimulates the 5-lipoxygenase (5-LOX) biosynthesis pathway in the endometrium, and findings indicate that neuropeptide Y (NPY) plays a role in regulating uterine function. The aim of the present study was to determine NPY receptor subtypes 1 (Y1R) and 2 (Y2R) mRNA and protein abundances in the inflamed porcine endometrium and NPY influence alone and with Y1R or Y2R antagonists on 5-LOX, leukotriene (LT)A4 hydrolase (LTAH) and LTC4 synthase (LTCS) protein abundances and LTB4 and LTC4 release from this tissue. Either saline solution (CON group) or Escherichia coli (E. coli) suspension (E. coli group) was injected into the uterine horns. After eight days, in the E. coli group, severe acute endometritis was diagnosed, along with decreased Y1R mRNA and protein abundances, and decreased Y2R mRNA abundance and increased Y2R protein abundance compared to the CON group. NPY increased 5-LOX, LTAH and LTCS protein abundances and LTB4 and LTC4 release from the endometrial stripes of both groups, while in the E. coli group, the above parameters were higher compared to the CON group. In both groups, the Y1R antagonist reduced NPY-induced 5-LOX and LTCS protein abundances in reference to NPY influence alone. This effect was also exerted by the Y1R antagonist combined with NPY on LTB4 release in the CON group and on LTAH protein abundance and LTC4 release in the E. coli group. As compared to NPY action alone, the Y2R antagonist with NPY caused a decrease in LTAH protein abundance and LTB4 and LTC4 release in both CON and E. coli groups. Summarizing, in the inflamed porcine endometrium changes Y1R and Y2R mRNA and protein abundances. NPY by interaction with Y1Rs and Y2Rs stimulates LTAH protein abundance and LTC4 release, and by acting through Y1Rs increases 5-LOX and LTCS protein abundances, and by Y2Rs increases LTB4 release. NPY can indirectly affect LT-regulated processes in an inflamed endometrium. Moreover, the NPY effect mediated by Y1Rs and Y2Rs on the 5-LOX pathway suggests the potential to use these receptors for therapeutic modulation of endometrial inflammation in animals and humans.