PSB 603 - a known selective adenosine A2B receptor antagonist - has anti-inflammatory activity in mice.

Abstract

A2B adenosine receptors are present in a wide spectrum of tissues, especially on cells of the immune system. Since these particular receptors have the lowest, of all adenosine receptor subtypes, affinity for adenosine they are believed to play a special role in immunological processes associated with elevated adenosine levels such as inflammation. The aim of this preliminary study was to determine the potential anti-inflammatory properties of compound PSB-603, a potent and selective adenosine A2B receptor antagonist, in two different experimental models of local and systemic inflammation. In a model of inflammation induced by local carrageenan administration paw edema was measured using a pletysmometer. Additionally, levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and reactive oxygen species (ROS) were determined in the inflamed paw. Using the mouse model of peripheral inflammation induced by intraperitoneal (ip) administration of zymosan A, the influence of the A2B antagonist on the infiltration of neutrophils into the peritoneum and its effect on the plasma levels of CRP, TNF-α, and IL-6 were investigated. The results showed that PSB-603 administered at a dose of 5 mg/kg b.w. ip significantly reduced inflammation in both tested models. Particularly, it significantly decreased levels of the inflammatory cytokines IL-6, TNF-α and of ROS in the inflamed paw and reduced inflammation of the peritoneum by significantly decreasing the infiltration of leukocytes. Additionally, in the latter model, no statistically significant difference was observed in the CRP level between the control group without inflammation and the group which has been treated with the PSB-603 compound. Thus, the results may indicate the anti-inflammatory activity of adenosine A2B receptor antagonists in two different models of inflammation.

• Authors: Magdalena Kotańska, Małgorzata Szafarz, Kamil Mika, Anna Dziubina, Marek Bednarski, Christa E Müller, Jacek Sapa, Katarzyna Kieć-Kononowicz
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 135 Pg. 111164 (Mar 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 33385856 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Adenosine A2 Receptor Antagonists
• Anti-Inflammatory Agents
• Cytokines
• Inflammation Mediators
• PSB603
• Reactive Oxygen Species
• Receptor, Adenosine A2B
• Sulfonamides
• Xanthines
• adora2b protein, mouse
• Carrageenan
• Zymosan

Topics

• Adenosine A2 Receptor Antagonists (pharmacology)
• Animals
• Anti-Inflammatory Agents (pharmacology)
• Carrageenan
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation (chemically induced, metabolism, prevention & control)
• Inflammation Mediators (metabolism)
• Male
• Mice
• Reactive Oxygen Species (metabolism)
• Receptor, Adenosine A2B (drug effects, metabolism)
• Signal Transduction
• Sulfonamides (pharmacology)
• Xanthines (pharmacology)
• Zymosan