Thromboxane A2 receptors in equine monocytes: identification of a new subclass of TXA2 receptors.
Abstract: Thromboxane (TX) A2 has been implicated as an important pathophysiologic mediator of a variety of cardiovascular diseases. Monocytes synthesize TXA2 and it modulates their function. This study sought to characterize monocyte TXA2 receptors. Radioligand binding studies were performed on membranes prepared from equine peripheral blood monocytes using [125I]BOP, a TXA2 receptor agonist. [125I]BOP bound to a single class of binding sites (Kd = 1.0 +/- 0.3 nM and Bmax = 389 +/- 191 fmol/mg protein; n = 5). Several TXA2 receptor agonists and antagonists competed for binding with [125I]BOP. I-BOP produced a concentration-dependent inhibition of endotoxin-induced tumor necrosis factor (TNF) activity (IC50 = 9.6 +/- 2.5 nM; n = 5). In contrast to its effects in platelets and vascular smooth muscle, I-BOP significantly increased cAMP formation in monocytes (EC50 = 22 +/- 3.6 nM; n = 4). The TXA2 receptor antagonists SQ29548 (5.6 microM) and L657925 (0.13 microM) significantly blocked I-BOP-stimulated cAMP formation but did not block 250 nM prostaglandin E2-stimulated cAMP formation. These data support the presence of a TXA2 receptor in equine peripheral blood monocytes. Activation of this receptor results in suppression of endotoxin-induced TNF formation and stimulation of cAMP production. Increased cAMP production after receptor activation suggests that this receptor may represent a unique subclass of TXA2 receptors.
Publication Date: 1993-02-01 PubMed ID: 8383167DOI: 10.1002/jlb.53.2.173Google Scholar: Lookup
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- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research paper is centered around exploring a new subclass of Thromboxane (TX) A2 receptors in equine monocytes.
Background
- Thromboxane (TX) A2 has been recognized as a significant mediator in various cardiovascular diseases.
- Monocytes, a type of white blood cell, can create TXA2, which influences their function.
- The study wishes to examine and categorize the TXA2 receptors that exist within these monocytes.
Methods and Observations
- For this study, scientists used [125I]BOP, an activator of the TXA2 receptor, to perform radioligand binding studies on membranes created from equine peripheral blood monocytes.
- The binding of [125I]BOP happened with one kind of binding site and several TXA2 receptor activators and inhibitors vied for this binding.
- I-BOP, one of these activators, led to a notable reduction of the tumor necrosis factor (TNF) activity prompted by endotoxins. However, I-BOP also considerably increased the formation of cAMP, a key cellular messenger, in the monocytes.
- The raise in cAMP production was unique to monocytes and was not observed in platelets and vascular smooth muscle, which also have TXA2 receptors.
Conclusion
- The study’s findings suggest that equine peripheral blood monocytes do indeed have TXA2 receptors. When activated, these receptors led to the suppression of TNF induced by endotoxins and the stimulation of the production of cAMP.
- This increased production of cAMP as a result of receptor activation suggests that this particular TXA2 receptor could be a unique subclass. Hence, this research helps in the better understanding of the TXA2 receptor and its role and functioning within equine monocytes.
Cite This Article
APA
Simmons TR, Cook JA, Moore JN, Halushka PV.
(1993).
Thromboxane A2 receptors in equine monocytes: identification of a new subclass of TXA2 receptors.
J Leukoc Biol, 53(2), 173-178.
https://doi.org/10.1002/jlb.53.2.173 Publication
Researcher Affiliations
- Department of Physiology, Medical University of South Carolina, Charleston 29425.
MeSH Terms
- Animals
- Binding, Competitive
- Bridged Bicyclo Compounds / blood
- Bridged Bicyclo Compounds / pharmacology
- Bridged Bicyclo Compounds, Heterocyclic
- Carbazoles / pharmacology
- Cell Membrane / metabolism
- Cell Separation
- Cyclic AMP / blood
- Fatty Acids, Unsaturated / blood
- Fatty Acids, Unsaturated / pharmacology
- Horses
- Hydrazines / pharmacology
- Iodine Radioisotopes
- Kinetics
- Monocytes / metabolism
- Radioligand Assay
- Receptors, Thromboxane / antagonists & inhibitors
- Receptors, Thromboxane / classification
- Receptors, Thromboxane / metabolism
- Tumor Necrosis Factor-alpha / biosynthesis
Grant Funding
- GM27673 / NIGMS NIH HHS
- HL02562 / NHLBI NIH HHS
- HL36838 / NHLBI NIH HHS
Citations
This article has been cited 2 times.- da Silva-Souza HA, de Lira MN, Patel NK, Spray DC, Persechini PM, Scemes E. Inhibitors of the 5-lipoxygenase pathway activate pannexin1 channels in macrophages via the thromboxane receptor.. Am J Physiol Cell Physiol 2014 Sep 15;307(6):C571-9.
- Thomas DW, Mannon RB, Mannon PJ, Latour A, Oliver JA, Hoffman M, Smithies O, Koller BH, Coffman TM. Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.. J Clin Invest 1998 Dec 1;102(11):1994-2001.
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