Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils.
Abstract: To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Methods: Neutrophils obtained from 10 healthy horses. Methods: An adenosine analogue (5'-N-ethylcarboxamidoadenosine [NECA]) was tested for its ability to inhibit production of reactive oxygen species (ROS) in LPS-stimulated equine neutrophils. Selective adenosine receptor antagonists were used to identify the receptor subtype responsible for effects. To assess the mechanism of action of NECA, cAMP concentrations were measured, and effects of dibutyryl cAMP (a stable analogue of cAMP) and rolipram (a type 4 phosphodiesterase inhibitor) were investigated. Results: NECA elicited concentration-dependent inhibition of ROS production that was inhibited by ZM241385, a selective adenosine A(2A) receptor antagonist; this effect of NECA was not affected by the adenosine A(2B) receptor antagonist MRS1706. Also, ZM241385 blocked NECA-induced increases in cAMP concentrations, whereas MRS1706 did not alter this effect of NECA. Rolipram potentiated NECA-induced inhibition of ROS production, and dibutyryl cAMP also inhibited ROS production. Conclusions: Activation of adenosine A(2A) receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. These results suggest that stable adenosine A(2A) receptor agonists may be developed as suitable anti-inflammatory drugs in horses.
Publication Date: 2007-06-05 PubMed ID: 17542699DOI: 10.2460/ajvr.68.6.649Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Adenosine Triphosphate (ATP)
- Anti-inflammatory
- Biochemistry
- Cells
- Clinical Study
- Disease Treatment
- Equine Diseases
- Equine Health
- Horses
- Immune Response
- Inflammation
- Inflammatory Response
- Lipopolysaccharide
- Neutrophils
- Pharmacodynamics
- Pharmacology
- Physiology
- Reactive Oxygen Species
- Veterinary Medicine
- Veterinary Research
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article investigates the anti-inflammatory effects of a certain adenosine analogue (NECA) on horse neutrophils stimulated by lipopolysaccharide (LPS), specifically its ability to inhibit the production of reactive oxygen species (ROS).
Research Methods and Materials
The research was implemented using neutrophils obtained from 10 healthy horses. The major substances used in the experiment were:
- Lipopolysaccharide (LPS): A molecule used to stimulate the neutrophils.
- 5′-N-ethylcarboxamidoadenosine (NECA): An adenosine analogue tested for its inhibitory effects on reactive oxygen species production.
- ZM241385 and MRS1706: Selective adenosine A(2A) and A(2B) receptor antagonists, respectively, used to identify the receptor subtype responsible for effects.
- Dibutyryl cAMP and Rolipram: These were used to investigate the mechanism of action of NECA, with rolipram being a type 4 phosphodiesterase inhibitor and dibutyryl cAMP is a stable analogue of cAMP.
Research Results and Observations
Throughout the experiments, several observations were noted:
- NECA showed a concentration-dependent inhibition of reactive oxygen species (ROS) production.
- The inhibitory effect of NECA was hampered by ZM241385, a selective adenosine A(2A) receptor antagonist. However, the adenosine A(2B) receptor antagonist MRS1706 did not affect NECA’s effect.
- NECA-induced increases in cAMP concentrations were blocked by ZM241385 but not by MRS1706.
- The study also revealed that rolipram enhanced the NECA-induced inhibition of ROS production, and dibutyryl cAMP also inhibited ROS production.
Conclusion and Implications of the Research
It was concluded from the study that activation of adenosine A(2A) receptors inhibits ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. This suggests that stable adenosine A(2A) receptor agonists could potentially be developed as useful anti-inflammatory drugs in horses, marking a significant potential development in equine medicine.
Cite This Article
APA
Sun WC, Moore JN, Hurley DJ, Vandenplas ML, Murray TF.
(2007).
Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils.
Am J Vet Res, 68(6), 649-656.
https://doi.org/10.2460/ajvr.68.6.649 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
MeSH Terms
- Adenosine A2 Receptor Agonists
- Adenosine A2 Receptor Antagonists
- Adenosine-5'-(N-ethylcarboxamide) / pharmacology
- Animals
- Cyclic AMP / metabolism
- Dose-Response Relationship, Drug
- Horses / metabolism
- Lipopolysaccharides / pharmacology
- Neutrophils / drug effects
- Neutrophils / metabolism
- Reactive Oxygen Species / metabolism
- Receptor, Adenosine A2A / metabolism
- Rolipram / pharmacology
- Triazines / pharmacology
- Triazoles / pharmacology
Citations
This article has been cited 7 times.- Bai Y, Zhang X, Zheng J, Liu Z, Yang Z, Zhang X. Overcoming high level adenosine-mediated immunosuppression by DZD2269, a potent and selective A2aR antagonist. J Exp Clin Cancer Res 2022 Oct 14;41(1):302.
- Haywood N, Byler MR, Zhang A, Rotar EP, Money D, Gradecki SE, Ta HQ, Salmon M, Kron IL, Laubach VE, Mehaffey JH, Roeser ME. Secondary Burn Progression Mitigated by an Adenosine 2A Receptor Agonist. J Burn Care Res 2022 Jan 5;43(1):133-140.
- Ryzhov S, May T, Dziodzio J, Emery IF, Lucas FL, Leclerc A, McCrum B, Lord C, Eldridge A, Robich MP, Ichinose F, Sawyer DB, Riker R, Seder DB. Number of Circulating CD 73-Expressing Lymphocytes Correlates With Survival After Cardiac Arrest. J Am Heart Assoc 2019 Jul 2;8(13):e010874.
- Martin EM, Schirmer JM, Jones SL, Davis JL. Pharmacokinetics and ex vivo anti-inflammatory effects of oral misoprostol in horses. Equine Vet J 2019 May;51(3):415-421.
- Grace PM, Gaudet AD, Staikopoulos V, Maier SF, Hutchinson MR, Salvemini D, Watkins LR. Nitroxidative Signaling Mechanisms in Pathological Pain. Trends Neurosci 2016 Dec;39(12):862-879.
- Burnstock G, Boeynaems JM. Purinergic signalling and immune cells. Purinergic Signal 2014 Dec;10(4):529-64.
- Trevethick MA, Mantell SJ, Stuart EF, Barnard A, Wright KN, Yeadon M. Treating lung inflammation with agonists of the adenosine A2A receptor: promises, problems and potential solutions. Br J Pharmacol 2008 Oct;155(4):463-74.
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