Effects of WEB 2086, an antagonist to the receptor for platelet-activating factor (PAF), on PAF-induced responses in the horse.
Abstract: Platelet-activating factor (PAF) causes oedema and neutrophil accumulation when injected into the skin of normal horses. PAF is also known to induce aggregation of horse platelets in vitro. The selective PAF receptor antagonist WEB 2086 has now been used to determine whether these effects are mediated by PAF receptor activation. Addition of WEB 2086 to equine platelets in vitro inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.14). Inhibition of in vivo inflammatory responses to PAF occurred after local administration of WEB 2086: wheal formation induced by 0.1 micrograms PAF/site was reduced by 1-10 micrograms WEB 2086/site. PAF (1 micrograms/site)-induced neutrophil accumulation was also inhibited by co-administration of 10 micrograms WEB 2086/site. Systemic administration of WEB 2086 (3 mg/kg iv) to 4 normal ponies inhibited PAF-induced wheal formation and ex vivo platelet aggregation. At 30 min after drug administration the concentration of PAF required to produce a half maximal aggregation response was increased 496 +/- 137 fold. At 6 h the degree of inhibition was markedly reduced and responses had returned to pre-treatment values by 24 h. PAF-induced increases in cutaneous vascular permeability were also reduced by 80% as early as 30 min after iv administration of WEB 2086 in these animals, the inhibition persisting for at least 6 h. These results suggest that in vitro and in vivo responses to PAF in the horse are mediated via activation to PAF receptors. WEB 2086 will therefore be a useful agent for studying the role of PAF in the pathogenesis of equine inflammatory conditions.
Publication Date: 1992-05-01 PubMed ID: 1318830DOI: 10.1111/j.2042-3306.1992.tb02815.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article explores the effects of WEB 2086, an antagonist to the Platelet-Activating Factor (PAF) receptor, on PAF-induced responses in horses. The study concludes that the in-vitro and in-vivo reactions to PAF in horses are mediated through the activation of PAF receptors, making WEB 2086 potentially useful for studying equine inflammatory conditions.
The Role of Platelet-Activating Factor (PAF)
- The effects of PAF, a compound known to cause oedema (swelling) and neutrophil accumulation in horses, are examined. PAF also induces aggregation (clumping together) of platelets in vitro (in a controlled lab environment).
The Effects of WEB 2086
- WEB 2086, a selective antagonist for the PAF receptor, is used to probe whether the effects of PAF are mediated by PAF receptor activation. An antagonist is a compound that inhibits or interferes with the physiological action of another.
- When WEB 2086 is added to horse platelets in vitro, it prevents PAF-induced aggregation in a manner that is competitive and reversible.
- WEB 2086 also inhibits in vivo (in the body or live animal) inflammatory reactions to PAF, reducing wheal (skin swelling) formation induced by PAF.
Inhibition of PAF-Induced Reactions
- Neutrophil accumulation induced by PAF is hindered by the co-administration of WEB 2086.
- Systemic (whole body) administration of WEB 2086 to ponies inhibits PAF-induced wheal formation and reduces ex vivo platelet aggregation (clumping of platelets outside the body but in a similar environment).
- There is an evident increase in the concentration of PAF required to produce a half maximal aggregation response after WEB 2086 administration. However, the degree of this inhibitory effect substantially reduces 6 hours post-treatment, and responses return to pre-treatment values after 24 hours.
- PAF-induced increases in skin vascular permeability, which contributes to oedema, are reduced by 80% as early as 30 minutes post IV administration of WEB 2086, with this inhibitory effect lasting for at least 6 hours.
Implications of the Research
- This research suggests that both in vitro and in vivo responses to PAF in horses are mediated through the activation of PAF receptors. This makes WEB 2086 a useful tool for studying the role of PAF in the development of equine inflammatory conditions such as laminitis or dermatitis.
Cite This Article
APA
Foster AP, Lees P, Andrews MJ, Cunningham FM.
(1992).
Effects of WEB 2086, an antagonist to the receptor for platelet-activating factor (PAF), on PAF-induced responses in the horse.
Equine Vet J, 24(3), 203-207.
https://doi.org/10.1111/j.2042-3306.1992.tb02815.x Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, Hatfield, Hertfordshire, UK.
MeSH Terms
- Animals
- Azepines / pharmacology
- Capillary Permeability / drug effects
- Cell Migration Inhibition
- Cell Movement / drug effects
- Dose-Response Relationship, Drug
- Horses / blood
- Horses / physiology
- Neutrophils / drug effects
- Platelet Activating Factor / antagonists & inhibitors
- Platelet Aggregation / drug effects
- Platelet Aggregation Inhibitors / pharmacology
- Platelet Membrane Glycoproteins
- Receptors, Cell Surface / antagonists & inhibitors
- Receptors, G-Protein-Coupled
- Triazoles / pharmacology
Citations
This article has been cited 4 times.- da Silva MB, Dessy C, Coghe J, David JL, Lekeux P. Protective effects of WEB 2086 (PAF antagonist) and ketoprofen (NSAID) on PAF-induced changes in the morphological ultrastructure of blood platelets in calves.. Vet Res Commun 1998 Jun;22(4):273-91.
- Bastos da Silva MB, Gustin P, Herion F, Raskinet R, David JL, Gougnard T, Plomteux G, Desmecht D, Lekeux P. The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.. Vet Res Commun 1997 Oct;21(7):521-31.
- Foster AP, Lees P, Cunningham FM. Actions of PAF receptor antagonists in horses with the allergic skin disease sweet itch.. Inflamm Res 1995 Oct;44(10):412-7.
- Koltai M, Braquet PG. Platelet-activating factor antagonists.. Clin Rev Allergy 1994 Winter;12(4):361-80.
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