Zerpa H, Bailey S R, Berhane Y, Elliott J
Department of Biomedical Sciences, Veterinary School, Faculty of Veterinary Science, Central University of Venezuela, Maracay, Aragua State, Venezuela.
J Vet Pharmacol Ther. 2006 Feb;29(1):55-61. doi: 10.1111/j.1365-2885.2006.00716.x.
Alpha-adrenoceptors mediate contractile responses in equine digital veins (EDVs) and arteries. Vascular smooth muscle alpha(1)-adrenoceptor subtypes have been implicated in a number of conditions, such as acute equine laminitis, and are therapeutic targets for the treatment of this condition. Digital veins, rather than arteries, were investigated in the present study because they have been specifically implicated in the pathophysiology of acute laminitis. The order of potency of a series of alpha(1)-adrenoceptor-selective agonists and antagonists was determined in isolated rings of EDVs under conditions of isometric tension. A61603 was the most potent agonist, with a higher potency (76-fold greater) than phenylephrine (PHE), suggesting the presence of the alpha(1A)-adrenoceptor subtype. Prazosin (30 nm) caused competitive inhibition of the responses to A61603 and PHE, with pK(b) values of 8.05 +/- 0.28 and 8.20 +/- 0.27, respectively. In addition, the alpha(1A)-adrenoceptor antagonist, WB4101 (10 nm), also caused competitive inhibition of the responses to the two agonists, with pK(b) values of 8.37 +/- 0.16 and 8.54 +/- 0.23, respectively, confirming the presence of the alpha(1A)-adrenoceptor subtype in EDVs. The selective alpha(1D)-adrenoceptor antagonist, BMY7378 (100 nm) did not cause a significant change in the response to the agonists, giving lower pK(b) values (6.97 +/- 0.27 and 6.88 +/- 0.17 vs. A61603 and PHE, respectively). Chloroethylclonidine dihydrochloride (45 microm, 30 min), used to produce selective inactivation of alpha(1B)-adrenoceptors, caused noncompetitive inhibition of the response to PHE, but was without effect on the response to A61603. These findings indicate that EDVs possess at least two different alpha(1)-adrenoceptor populations, which are predominantly of the alpha(1A) and alpha(1B) subtypes. These data may assist in the development of more selective antagonists for therapeutic use in horses.
α-肾上腺素能受体介导马趾静脉（EDV）和动脉的收缩反应。血管平滑肌α(1)-肾上腺素能受体亚型与多种病症有关，如急性马属动物蹄叶炎，并且是治疗该病症的治疗靶点。在本研究中对趾静脉而非动脉进行了研究，因为它们在急性蹄叶炎的病理生理学中具有特殊意义。在等长张力条件下，在分离的EDV环中测定了一系列α(1)-肾上腺素能受体选择性激动剂和拮抗剂的效价顺序。A61603是最有效的激动剂，其效价比去氧肾上腺素（PHE）高（高76倍），表明存在α(1A)-肾上腺素能受体亚型。哌唑嗪（30 nM）对A61603和PHE的反应产生竞争性抑制，pK(b)值分别为8.05±0.28和8.20±0.27。此外，α(1A)-肾上腺素能受体拮抗剂WB4101（10 nM）也对两种激动剂的反应产生竞争性抑制，pK(b)值分别为8.37±0.16和8.54±0.23，证实了EDV中存在α(1A)-肾上腺素能受体亚型。选择性α(1D)-肾上腺素能受体拮抗剂BMY7378（100 nM）对激动剂的反应未引起显著变化，pK(b)值较低（分别为6.
