title: Role of Dopamine and D2 Dopamine Receptor in the Pathogenesis of Inflammatory Bowel Disease.
abstract: BACKGROUND
  VEGF-induced vascular permeability and blood vessels remodeling are key features of inflammatory bowel disease (IBD) pathogenesis. Dopamine through D2 receptor (D2R) inhibits VEGF/VPF-mediated vascular permeability and angiogenesis in tumor models. In this study, we tested the hypothesis that pathogenesis of IBD is characterized by the disturbance of dopaminergic system and D2R activity.
  
  
  METHODS
  IL-10 knockout (KO) mice and rats with iodoacetamide-induced ulcerative colitis (UC) were treated intragastrically with D2R agonists quinpirole (1 mg/100 g) or cabergoline (1 or 5 µg/100 g). Macroscopic, histologic, and clinical features of IBD, colonic vascular permeability, and angiogenesis were examined.
  
  
  RESULTS
  Although colonic D2R protein increased, levels of tyrosine hydroxylase and dopamine transporter DAT decreased in both models of IBD. Treatment with quinpirole decreased the size of colonic lesions in rats with iodoacetamide-induced UC (p < 0.01) and reduced colon wet weight in IL-10 KO mice (p < 0.05). Quinpirole decreased colonic vascular permeability (p < 0.001) via downregulation of c-Src and Akt phosphorylation. Cabergoline (5 µg/100 g) reduced vascular permeability but did not affect angiogenesis and improved signs of iodoacetamide-induced UC in rats (p < 0.05).
  
  
  CONCLUSIONS
  Treatment with D2R agonists decreased the severity of UC in two animal models, in part, by attenuation of enhanced vascular permeability and prevention of excessive vascular leakage. Hence, the impairment dopaminergic system seems to be a feature of IBD pathogenesis.
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA. gtolstanova@gmail.com.|Educational-Scientific Center "Institute of Biology", Taras Shevchenko National University of Kyiv, Kiev, Ukraine. gtolstanova@gmail.com.
authors.forename: Ganna
authors.initials: G
authors.lastname: Tolstanova
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA.
authors.forename: Brankica
authors.initials: B
authors.lastname: Paunovic
authors.affiliation: Educational-Scientific Center "Institute of Biology", Taras Shevchenko National University of Kyiv, Kiev, Ukraine.
authors.forename: Alona
authors.initials: A
authors.lastname: Prysiazhniuk
authors.affiliation: Educational-Scientific Center "Institute of Biology", Taras Shevchenko National University of Kyiv, Kiev, Ukraine.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Ostapchenko
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tarnawski
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Sandor
authors.affiliation: VA Long Beach Healthcare System, Departments of Medicine, Pathology and Pharmacology, VA Medical Center (05/113), University of California-Irvine, 5901 East 7th Street, Long Beach, CA, 90822, USA. sszabo@uci.edu.
authors.forename: Sandor
authors.initials: S
authors.lastname: Szabo
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D015153:Blotting, Western; D000077465:Cabergoline; D002199:Capillary Permeability / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism*; D007460:Iodoacetamide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019257:Quinpirole / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D004873:Ergolines; D018836:Inflammation Mediators; D017448:Receptors, Dopamine D2; D016753:Interleukin-10; D019257:Quinpirole; D000077465:Cabergoline; D004298:Dopamine; D007460:Iodoacetamide
keywords: Animal models; D2 dopamine receptor; Dopamine; Inflammatory bowel disease; Vascular permeability