Histamine has the ability to influence the activity of immune cells including neutrophils and plays a pivotal role in inflammatory processes, which are a complex network of cellular and humoral events. One of the main functions manifested by activated neutrophils is oxidative burst, which is linked to the production of reactive oxygen species; therefore, the effects of histamine receptor agonists and antagonists on the oxidative burst of neutrophils is reviewed. A role for the well-characterized histamine H1 and H2 receptors in this process is discussed and compared to that of the recently discovered H4 receptor.

• Klíčová slova
• histamine, histamine receptor, neutrophil, oxidative burst, reactive oxygen species,
• MeSH
• agonisté histaminu farmakologie   MeSH
• antihistaminika farmakologie   MeSH
• histamin metabolismus   MeSH
• histaminový receptor H4 MeSH
• lidé MeSH
• neutrofily metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptory histaminu H1 účinky léků   metabolismus   MeSH
• receptory histaminu H2 účinky léků   metabolismus   MeSH
• receptory histaminu účinky léků   metabolismus   MeSH
• receptory spřažené s G-proteiny účinky léků   metabolismus   MeSH
• respirační vzplanutí účinky léků   MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• agonisté histaminu MeSH
• antihistaminika MeSH
• histamin MeSH
• histaminový receptor H4 MeSH
• HRH4 protein, human MeSH Prohlížeč
• reaktivní formy kyslíku MeSH
• receptory histaminu H1 MeSH
• receptory histaminu H2 MeSH
• receptory histaminu MeSH
• receptory spřažené s G-proteiny MeSH

As reported in our previous studies, dithiaden (an antagonist of histamine H(1)-receptor, used clinically as an anti-allergic or anti-emetic drug) in a concentration range of 5×10(-5)-10(-4) M decreased the production of reactive oxygen species by phagocytes. In this study we investigated the influence of dithiaden on nitric oxide (NO) production by LPS-stimulated macrophages.The cell viability in the presence of 10(-4)-5×10(-5) M dithiaden was evaluated by an ATP-test. RAW 264.7 cells (2.5×10(6)/well) were preincubated with dithiaden for 60 mins and subsequently stimulated with 0.1 µg/ml of bacterial lipopolysaccharide. After incubating for 24 hours the NO production was determined spectrophotometrically using Griess reaction as a concentration of nitrites (the end product of NO metabolism) accumulated in the cell supernatants. The expression of inducible nitric oxide synthase (iNOS) in cell-lysates was evaluated using Western blot analysis. Scavenging properties of dithiaden against NO were evaluated amperometrically.Our data demonstrate that dithiaden in the concentration of 5×10(-5) M (approved by ATP test as non toxic) caused a significant decrease in the accumulation of nitrites, and in addition, this decline was followed by a marked reduction of iNOS protein expression. Amperometrical analysis did not show any scavenging properties of dithiaden against NO.From this data it can be suggested that the inhibition effect of dithiaden on macrophage NO production is caused exclusively by the suppression of iNOS protein expression.

• Klíčová slova
• RAW 264.7 cells, dithiaden, inducible nitric oxide synthase, lipopolysaccharide, nitric oxide, nitrites,
• Publikační typ
• časopisecké články MeSH