Publication details
EFFECTS OF HISTAMINE AND ITS H4 RECEPTOR AGONISTS ON REACTIVE OXYGEN SPECIES PRODUCTION IN HUMAN LEUKOCYTES
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| Year of publication | 2013 |
| Type | Conference abstract |
| Citation | |
| Description | Histamine, an endogenous biogenic amine, is an important chemical messenger which has numerous physiological roles in central and peripheral tissues. These effects are mediated via four histamine receptors - H1R, H2R, H3R and H4R, which belong to the superfamily of G protein-coupled receptors. We investigated the effects of histamine and specific H4R agonists 4-methylhistamine and VUF8430 on the production of reactive oxygen species (ROS) in human whole blood and isolated leukocytes. Antioxidant parameters of histamine receptor agonists were investigated using total peroxyl radical-trapping antioxidant parameter analysis, oxygen radical absorbance capacity assay and NO-scavenging determination. Determination of ATP activity was used for evaluation of cell viability. The ability of isolated leukocytes or leukocytes in the whole blood of healthy human volunteers to produce ROS after histamine or its H4R agonist treatment (10-8 – 10-4 M) was tested by luminol-enhanced chemiluminescence, spontaneous or activated by opsonised zymosan particles (OZP) or phorbol-myristate-acetate (PMA). None of the studied compounds had any antioxidant potential against ROS. All three compounds significantly decreased the spontaneous and OZP-activated chemiluminescence response in whole blood leukocytes in a dose dependent manner. On the other hand, only VUF8430 was dose-dependently effective when whole blood leukocytes were activated with PMA. Generally, the effects of all three compounds were similar but less profound in isolated leukocytes. It can be concluded from our results and the literature that the inhibition of ROS production by tested compounds was most probably caused by H2R rather than by H4R. Especially at high concentrations of histamine the signal is transduced mainly through H2R and may inhibit the ROS production. Supported by grant LD11010 of the Ministry of Education, Youth and Sports of the Czech Republic and by COST BM0806 Action. |