Functional role of alpha2-adrenoceptor subtypes in the cooling-enhanced vasoconstriction of isolated cutaneous digital veins of the horse.
Abstract: Cooling-enhanced contractile responses in cutaneous arteries have been reported to involve the activation of alpha(2C)-adrenoceptors, but their role in cutaneous veins is not clearly understood. The aim was to pharmacologically characterize the subtype of postsynaptic alpha(2)-adrenoceptors in the equine digital vein mediating contraction at two temperatures. The increase in isometric tension of endothelium-denuded equine digital vein in response to UK-14304 was studied in the absence and presence of relatively selective alpha(2)-adrenoceptor antagonists at temperatures of either 30 degrees C (the peripheral digit temperature of horses maintained in a thermoneutral environment) or 22 degrees C. The response to UK-14304 was enhanced by cooling and antagonised by RX-821002 (alpha(2)-adrenoceptor non-selective; 30 degrees C: apparent pK(b)=8.5; 22 degrees C: pK(b)=8.2) and yohimbine (alpha(2)-adrenoceptor non-selective; 30 degrees C: apparent pK(b)=7.2; 22 degrees C: apparent pK(b)=7.4). The response at 30 degrees C was non-surmountably antagonised by BRL-44408 (alpha(2A)-adrenoceptor-selective; apparent pK(b)=8.9) and MK-912 (alpha(2C)-adrenoceptor-selective: apparent pK(b)=9.9). JP-1302 (alpha(2C)-adrenoceptor-selective) surmountably antagonised the response with a low potency (apparent pK(b)=5.6) at 30 degrees C. The response at 22 degrees C was surmountably antagonised by: BRL-44408 (alpha(2A)-adrenoceptor-selective; apparent pK(b)=6.5); MK-912 (alpha(2C)-adrenoceptor-selective; pK(b)=9.7) and JP-1302 (alpha(2C)-adrenoceptor-selective; apparent pK(b)=7.5). ARC-239 (alpha(2B)-adrenoceptor-selective) did not affect the response at either temperature. The apparent potency of the different antagonists and their non-surmountable effect, suggests that the UK-14304 response at 30 degrees C could be mediated by alpha(2A)-adrenoceptors and alpha(2C)-adrenoceptors. By contrast, the alpha(2C)-adrenoceptor appears to be the main alpha(2)-adrenoceptor mediating the augmented response at 22 degrees C. It is unlikely that the alpha(2B)-adrenoceptor subtype contributes at either temperature. These results support the participation of the alpha(2C)-adrenoceptors in the cooling-enhanced response to UK-14304 in this cutaneous vein.
Copyright (c) 2009 Elsevier B.V. All rights reserved.
Publication Date: 2009-10-28 PubMed ID: 19878669DOI: 10.1016/j.ejphar.2009.10.046Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the influence of alpha-2 adrenoceptors on the contraction of veins in horse skin when temperatures fall. The findings suggest that varying subtypes of these adrenoceptors could be involved at different temperatures, providing further insights into vascular function under different environmental temperatures.
Objective of the Study
- The study seeks to better understand the role that alpha2-adrenoceptors play in the cooling-enhanced contractile response in cutaneous veins. Prior studies have found an involvement of alpha2C-adrenoceptors in cutaneous arteries, thus this research aims to explore a similar involvement, but in cutaneous veins.
Methods Used
- The researchers conducted their studies on endothelium-denuded equine digital vein in response to the drug UK-14304. This substance has been used to stimulate the alpha2-adrenoceptors in the equine digital vein.
- The studies were conducted at two temperatures: at 30 degrees Celsius, which represents horses’ peripheral digit temperature in a thermoneutral environment, and at 22 degrees Celsius.
- Alongside, they used various antagonist substances, including RX-821002, yohimbine, BRL-44408, MK-912, JP-1302, and ARC-239, to observe their effect on the UK-14304 response under both temperature conditions. These antagonists have varying degrees of affinity for different subtypes of alpha2-adrenoceptors.
Results
- It was discovered that the contractile response to UK-14304 is enhanced when cooled, and this increase can be inhibited by both RX-821002 and yohimbine.
- At a temperature of 30 degrees Celsius, the UK-14304 response was non-surmountably antagonised by BRL-44408 and MK-912. In contrast, JP-1302 was found to surmountably antagonise the response with a low potency.
- At a temperature of 22 degrees Celsius, the response was surmountably antagonised by BRL-44408, MK-912, and JP-1302, but ARC-239 did not affect the response at either temperature.
- Based on these results, the researchers suggest that at 30 degrees Celsius the response could be mediated by alpha2A-adrenoceptors and alpha2C-adrenoceptors. However, at 22 degrees Celsius, the alpha2C-adrenoceptor appears to be the primary mediator of the response. The alpha2B-adrenoceptor subtype is not likely to contribute at either temperature.
Conclusion
- Overall, the study supports that alpha2C-adrenoceptors play a crucial role in the cooling-enhanced response to UK-14304 in the cutaneous vein. This research contributes to our understanding of how different adrenoceptor subtypes interact with temperature changes, which could further elucidate the physiological adaptation to environmental temperature changes in these animals.
Cite This Article
APA
Zerpa H, Berhane Y, Elliott J, Bailey SR.
(2009).
Functional role of alpha2-adrenoceptor subtypes in the cooling-enhanced vasoconstriction of isolated cutaneous digital veins of the horse.
Eur J Pharmacol, 627(1-3), 194-202.
https://doi.org/10.1016/j.ejphar.2009.10.046 Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, United Kingdom.
MeSH Terms
- Adrenergic alpha-2 Receptor Antagonists
- Animals
- Brimonidine Tartrate
- Cold Temperature
- Horses
- Protein Subunits / antagonists & inhibitors
- Protein Subunits / metabolism
- Quinoxalines / pharmacology
- Receptors, Adrenergic, alpha-2 / metabolism
- Skin / blood supply
- Substrate Specificity
- Vasoconstriction / drug effects
- Veins / drug effects
- Veins / metabolism
- Veins / physiology
Citations
This article has been cited 2 times.- Klotz JL, McDowell KJ. Tall fescue ergot alkaloids are vasoactive in equine vasculature.. J Anim Sci 2017 Nov;95(11):5151-5160.
- Jantschak F, Pertz HH. Alpha2C-adrenoceptors play a prominent role in sympathetic constriction of porcine pulmonary arteries.. Naunyn Schmiedebergs Arch Pharmacol 2012 Jun;385(6):595-603.
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