title: 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.
authors.affiliation: Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, United Kingdom.
authors.forename: Hector
authors.initials: H
authors.lastname: Zerpa
authors.forename: Yoel
authors.initials: Y
authors.lastname: Berhane
authors.forename: Jonathan
authors.initials: J
authors.lastname: Elliott
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bailey
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D000068438:Brimonidine Tartrate; D003080:Cold Temperature; D006736:Horses; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012867:Skin / Q000098:blood supply*; D013379:Substrate Specificity; D014661:Vasoconstriction / Q000187:drug effects; D014680:Veins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D021122:Protein Subunits; D011810:Quinoxalines; D018341:Receptors, Adrenergic, alpha-2; D000068438:Brimonidine Tartrate