Proceedings of The Physiological Society

Future Physiology (Leeds, UK) (2017) Proc Physiol Soc 39, PC49

Poster Communications

The role of D3R in colonic mucus secretion during experimental colitis in rats

A. Prysiazhniuk1, T. Dovbynchuk1, Y. Holota1, I. Vareniuk1, L. Garmanchuk1, G. Tolstanova1

1. Taras Shevchenko National University of Kyiv, Kyiv, Kyiv, Ukraine.

Introduction. Our previous study showed that activation of D3 dopamine receptors (D3R) had the beneficial effect in experimental colitis treatment while the mechanism of this effect is unclear. The disruption of surface colon mucosa layer with subsequent activation of local immune response by the bacterial infiltration into the inner layer of the mucosa are the key pathogenic mechanism of ulcerative colitis progression and perpetuation. We found the localization of D3R on the Goblet cells in colonic mucosa. In present study we tested the hypothesise that activation of D3R improves colonic mucus secretion during experimental colitis. Methods. Study was done on male Wistar rats (180-230). Experimental colitis was induced by 6% iodoacetamide (IA) (0,1 ml, enema). Selective D3R agonist 7-OH-DPAT (0.02 mg/100 g, s.c.) was injected 0,5 h prior to IA enema. Rats were euthanized 0,5 and 2 h after IA enema. During the autopsy 7 cm colon from the anus has been removed. Surface mucus layer was separated from epithelial cells with N-acetyl-L-cysteine and glycoproteins was measured by periodic acid/Schiff (PAS) staining or by the reaction with Folin reagent. The content of hexose, fucose and hexosamine were determined by standard biochemical assays. Morphometric analysis was performed to evaluate the histological changes of colonic epithelial and Goblet cells. Oxidative metabolism and arginase activity (analyzed by colorimetric method) in peritoneal macrophages were investigated. Result. Pre-treatment with 7-OH-DPAT did not affect the glycoprotein levels in normal mucosa, but significantly increased total levels of glycoprotein (1,6-fold, p<0.05) and hexose (1,1-fold, p<0.05) during IA-colitis. Furthermore, 7-OH-DPAT significantly increased functional reserve of peritoneal macrophages in 0,5 h (1,6-fold, p<0.05) and in 2 h (1,3-fold, p<0.05) after IA enema. Pre-treatment with 7-OH-DPAT decreased the mucosal layer thickness 1,1-fold (p<0.05), crypt depth 1,1-fold (p<0.05) and Goblet cell intersection area 1,2-fold (p<0.05) after IA enema. Conclusion. Pre-treatment with D3R-agonist increased levels of mucus secretion and activated natural immune response by macrophage activation during experimental colitis, which could indicate about the protective role of D3R.

Where applicable, experiments conform with Society ethical requirements