Abstract
We investigated the involvement of central and peripheral D2 dopaminergic receptors in the mechanism of vascular permeability in rat's colon during experimental ulcerative colitis. Ulcerative colitis was induced in male white inbred rats by 6 % iodoacetamide enema. For the investigation of central and peripheral D2R, separate and joint injections of D2R antagonist domperidone (2 mg/100 g, per os) and D2R agonist quinpirole (1 mg/100 g, per os) were applied. Central D2R were destroyed by neurotoxin injection – 6OHDA. Colonic vascular permeability was measured by colonic extravasation of 1,5 % Evans blue. It was observed that blockade of peripheral D2R decreased colonic vascular permeability, while simultaneous activation of central D2R and inhibition of peripheral D2R have additive positive effect in prevention of increased colonic vascular permeability during experimental colitis.
Highlights
Inflammatory bowel diseases (IBD) dopamine receptors – D1 class, which consist of D1 and development in human, as well as in animal models, is D5 subtypes and D2 class, which consists of D2, D3 and usually supported by increase of vascular permeability, D4 subtypes
Many of the cytokines, deregulated during IBD pathogenesis, are pro-angiogenic: e.g., IL-17, which is synthesized by invasive Th17 cells and TNFα, which is synthesized by macrophages, monocytes and endothelial cells [1]
Tumour angiogenesis was inhibited by D2R agonist via abrogation VEGFR-2-mediated signalling in endothelial cells [13]
Summary
Inflammatory bowel diseases (IBD) dopamine receptors – D1 class, which consist of D1 and development in human, as well as in animal models, is D5 subtypes and D2 class, which consists of D2, D3 and usually supported by increase of vascular permeability, D4 subtypes. Expression of D1, D2, D3 and D5 dopamine which leads to the tissue edema Number of mediators such as angiotenin, chemokines (IL-8, IL-10), coagulation factors, cytokines (IFN-γ, IL-13) and growth factors, mainly vascular endothelial growth factor (VEGF), affect vascular permeability and angiogenic balance. Three different types of vascular permeability were previously defined: basal vascular permeability of normal tissues, acute vascular hyperpermeability, chronic hyperpermeability, which is typical for pathological angiogenesis. While basal permeability is most typical for capillaries because of their structure, acute vascular hyperpermeability appears in postcapillary venules in response to single or short-term influence of VEGF, histamine, serotonine etc. Under the constant influence of permeabilityincreasing factors, deep changes in venules structure and functioning appear, which lead to the chronic hyperpermeability and pathologic angiogenesis [3]. Determination of glucose and glucose tolerance test is an important in period of prevention or treatment obesity
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