Tag Archives: granulocytes

Role of peripheral dopaminergic system in the pathogenesis of experimental colitis in rats

A. I. Prysiazhniuk, M. P. Rudyk, T. M. Chervinska, T. V. Dovbynchuk,
I. V. Opeida, L. M. Skivka, G. M. Tolstanova

Taras Shevchenko National University of Kyiv, Ukraine;
e-mail: gtolstanova@gmail.com

Dopamine (DA) is produced and released by immune cells. Recent data pointed to DA as a key mediator between the nervous and immune systems. In the present study we tested the hypothesis that peripheral dopaminergic system plays a negative role in ulcerative colitis pathogenesis via the effect on activity of peripheral blood phagocytes. The study was conducted on male Wistar rats (170-200 g). The peripheral dopaminergic system was destroyed by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection (20 mg/kg, s.c., 4 times every 2 h). Colitis was induced by 0.1 ml 6% iodoacetamide enema. Rats were subjected to autopsy on the 18th day. We found that MPTP-treated rats had decreased levels of tyrosine hydroxylase, rate-limiting enzyme of DA synthesis, in colon but not in brain. The number and activity of colonic and peripheral blood granulocytes did not significantly differ in saline- and MPTP-treated rats with colitis. The decreased ROS production by monocytes; increased 1.8-fold the number of CD69 (an early activation marker) positive monocytes and 6-fold intensity of CD69 surface expression were observed in MPTP-treated rats vs. saline-treated rats during colitis. The CD14 (the endotoxin coreceptor of phagocytes) surface expression was 2-fold increased in MPTP-treated rats without colitis, but significantly decreased in both saline- and MPTP-treated rats with colitis. We showed for the first time that the destruction of peripheral dopaminergic neurons leads to the improvement of morphological signs of experimental colitis, which might be through the regulatory effect of dopaminergic system on monocytes phenotype and their respiratory burst activity.