Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils

Wan Chun Sun, James N. Moore, David J. Hurley, Michel L. Vandenplas, Thomas F. Murray

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Objective - To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Sample Population - Neutrophils obtained from 10 healthy horses. Procedures - 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 A2A receptor antagonist; this effect of NECA was not affected by the adenosine A2B 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 and Clinical Relevance - Activation of adenosine A2A receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. These results suggest that stable adenosine A2A receptor agonists may be developed as suitable anti-inflammatory drugs in horses.

Original languageEnglish
Pages (from-to)649-656
Number of pages8
JournalAmerican Journal of Veterinary Research
Volume68
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Adenosine-5'-(N-ethylcarboxamide)
Adenosine A2A Receptors
adenosine
lipopolysaccharides
Horses
Lipopolysaccharides
neutrophils
reactive oxygen species
Reactive Oxygen Species
Neutrophils
horses
receptors
Adenosine A2 Receptor Antagonists
Rolipram
antagonists
Adenosine
Anti-Inflammatory Agents
Adenosine A2 Receptor Agonists
Phosphodiesterase 4 Inhibitors
Purinergic P1 Receptor Antagonists

All Science Journal Classification (ASJC) codes

  • veterinary(all)

Cite this

Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils. / Sun, Wan Chun; Moore, James N.; Hurley, David J.; Vandenplas, Michel L.; Murray, Thomas F.

In: American Journal of Veterinary Research, Vol. 68, No. 6, 06.2007, p. 649-656.

Research output: Contribution to journalArticle

@article{9eef8b9da5274f689ddcb7fb2aa75f9c,
title = "Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils",
abstract = "Objective - To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Sample Population - Neutrophils obtained from 10 healthy horses. Procedures - 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 A2A receptor antagonist; this effect of NECA was not affected by the adenosine A2B 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 and Clinical Relevance - Activation of adenosine A2A receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. These results suggest that stable adenosine A2A receptor agonists may be developed as suitable anti-inflammatory drugs in horses.",
author = "Sun, {Wan Chun} and Moore, {James N.} and Hurley, {David J.} and Vandenplas, {Michel L.} and Murray, {Thomas F.}",
year = "2007",
month = "6",
doi = "10.2460/ajvr.68.6.649",
language = "English",
volume = "68",
pages = "649--656",
journal = "American Journal of Veterinary Research",
issn = "0002-9645",
publisher = "American Veterinary Medical Association",
number = "6",

}

TY - JOUR

T1 - Effects of stimulation of adenosine A2A receptors on lipopolysaccharide-induced production of reactive oxygen species by equine neutrophils

AU - Sun, Wan Chun

AU - Moore, James N.

AU - Hurley, David J.

AU - Vandenplas, Michel L.

AU - Murray, Thomas F.

PY - 2007/6

Y1 - 2007/6

N2 - Objective - To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Sample Population - Neutrophils obtained from 10 healthy horses. Procedures - 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 A2A receptor antagonist; this effect of NECA was not affected by the adenosine A2B 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 and Clinical Relevance - Activation of adenosine A2A receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. These results suggest that stable adenosine A2A receptor agonists may be developed as suitable anti-inflammatory drugs in horses.

AB - Objective - To assess the anti-inflammatory effects of an adenosine analogue on lipopolysaccharide (LPS)-stimulated equine neutrophils. Sample Population - Neutrophils obtained from 10 healthy horses. Procedures - 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 A2A receptor antagonist; this effect of NECA was not affected by the adenosine A2B 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 and Clinical Relevance - Activation of adenosine A2A receptors inhibited ROS production by LPS-stimulated equine neutrophils in a cAMP-dependent manner. These results suggest that stable adenosine A2A receptor agonists may be developed as suitable anti-inflammatory drugs in horses.

UR - http://www.scopus.com/inward/record.url?scp=34447334160&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447334160&partnerID=8YFLogxK

U2 - 10.2460/ajvr.68.6.649

DO - 10.2460/ajvr.68.6.649

M3 - Article

C2 - 17542699

AN - SCOPUS:34447334160

VL - 68

SP - 649

EP - 656

JO - American Journal of Veterinary Research

JF - American Journal of Veterinary Research

SN - 0002-9645

IS - 6

ER -