Piascik M T, Guarino R D, Smith M S, Soltis E E, Saussy D L, Perez D M
Department of Pharmacology, College of Medicine, University of Kentucky, Lexington, USA.
J Pharmacol Exp Ther. 1995 Dec;275(3):1583-9.
With a selective antagonist, the specific contribution of the alpha-1D adrenoceptor (AR) to vascular smooth muscle contraction has been assessed. BMY 7378 bound to membranes expressing the cloned rat alpha-1D AR with a > 100-fold higher affinity (K1 = 2 nM) than binding to either the cloned rat alpha-1A AR (Ki = 800 nM) or the hamster alpha-1B AR (Ki = 600 nM). BMY 7378 exhibited differential potency in inhibiting vascular smooth muscle contraction. In the rat aorta and iliac artery, BMY 7378 was a high-affinity antagonist, producing parallel shifts in the phenylephrine concentration-response curve. The dissociation constants for this compound by Schild analysis were 0.95 and 4 nM for the aorta and iliac artery, respectively. The slopes of these Schild plots were not significantly different from unity. BMY 7378 was a weak antagonist in the rat caudal, mesenteric resistance and renal arteries, with Schild slopes significantly < 1. With ribonuclease protection assays, alpha-1D mRNA was found in all blood vessels examined. These data suggest that (1) BMY 7378 is a selective alpha-1D AR antagonist that can be used in functional systems to assess the contribution of this receptor in vascular smooth muscle contraction; (2) the alpha-1D AR appears to play a major role in the contraction of the aorta and iliac artery; (3) despite the fact that the mRNA for the alpha-1D AR can be detected in the caudal, mesenteric resistance (4) and renal arteries, it does not appear to play a role in mediating contraction of these blood vessels; and (4) expression of alpha-1D mRNA in a particular artery does not ensure that this receptor is involved in regulating the contraction of that artery.
使用选择性拮抗剂，已评估了α-1D肾上腺素能受体（AR）对血管平滑肌收缩的具体作用。BMY 7378与表达克隆大鼠α-1D AR的膜结合，其亲和力（K1 = 2 nM）比与克隆大鼠α-1A AR（Ki = 800 nM）或仓鼠α-1B AR（Ki = 600 nM）的结合亲和力高100倍以上。BMY 7378在抑制血管平滑肌收缩方面表现出不同的效力。在大鼠主动脉和髂动脉中，BMY 7378是一种高亲和力拮抗剂，使去氧肾上腺素浓度-反应曲线平行右移。通过Schild分析，该化合物在主动脉和髂动脉中的解离常数分别为0.95和4 nM。这些Schild图的斜率与1无显著差异。BMY 7378在大鼠尾动脉、肠系膜阻力动脉和肾动脉中是一种弱拮抗剂，Schild斜率显著<1。通过核糖核酸酶保护试验，在所有检测的血管中均发现了α-1D mRNA。这些数据表明：（1）BMY 7378是一种选择性α-1D AR拮抗剂，可用于功能系统中评估该受体在血管平滑肌收缩中的作用；（2）α-1D AR似乎在主动脉和髂动脉收缩中起主要作用；（3）尽管在尾动脉、肠系膜阻力动脉和肾动脉中可检测到α-1D AR的mRNA，但它似乎在介导这些血管的收缩中不起作用；（4）特定动脉中α-1D mRNA的表达并不确保该受体参与调节该动脉的收缩。
