Impaired Peripheral Dopaminergic System in Patients with Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is the chronic inflammatory disease unknown etiology. Little is known on the role of dopaminergic system in the pathogenesis of UC, despite the evidence that dopaminergic hypoactivity may result in excessive inflammation. We demonstrated a diminished risk for UC in patients with schizophrenia (hyper‐dopaminergic system) (Tolstanova G. et al. Gastroenterology 2010;138 (5):S‐264). In this study we tested the hypothesize that patients with chronic UC is characterized by the disturbance of peripheral dopaminergic system.MethodsColonic biopsy samples from 7 patients with chronic UC with recurrence stage and 7 ‐ from healthy colon were included in the study. Expressions and localization of D2, D3 dopamine receptors, DAT (responsible for dopamine re‐uptake) and tyrosine hydroxylase (TH, rate‐limiting enzyme of dopamine synthesize) were investigated with immunohistochemistry.ResultsProfound expression of DАТ, D2R, D3R and ТН was found in apical membrane of colonocytes and basal membrane of Goblet cells of healthy colonic mucosa. Inflamed colonic mucosa of patients with UC was characterized by 25% decrease in levels of D2R and D3R; 75% decrease levels of TH, mostly in colonocytes. Levels and localization of DAT was not significantly changed. ConclusionRecurrence of chronic UC is associated with the downregulation of dopamine synthesize, D2R and D3R expression in colonic mucosa. Restitution of dopaminergic system may be new molecular targets for the UC therapy. Study was supported by the grant 01BF‐03601 MES of Ukraine.