Bogoni G, Rizzi A, Calo G, Campobasso C, D'Orleans-Juste P, Regoli D
Institute of Pharmacology, University of Ferrara, Italy.
Br J Pharmacol. 1996 Dec;119(8):1600-4. doi: 10.1111/j.1476-5381.1996.tb16078.x.
The aim of the present study was to characterize pharmacologically endothelin receptors that are present in human umbilical vessels. 2. Endothelin-1 (ET-1) and endothelin-2 (ET-2) are potent stimulants of both the human umbilical artery (pEC50 7.9 and 7.5) and vein (pEC50 8.1 and 8.0). Endothelin-3 (ET-3) is inactive on the artery but contracts the vein (pEC50 7.6). IRL1620 is inactive in both vessels. The order of potency of agonists is suggestive of a typical ET(A) receptor in the artery (ET-1 = ET-2 > > ET-3) and a mixture of ET(A) and ET(B) receptors in the vein (ET-1 = ET-2 > or = ET-3). 3. The selective ET(A) receptor antagonist, BQ123, competitively inhibits the effect of ET-1 in the human umbilical artery (pA2 6.9), while in the vein, only a mixture of BQ123 and BQ788 (a selective ET(B) antagonist) weakly displaces to the right of the cumulative concentration-response curve to ET-1. Contractions induced by ET-3 in the vein are inhibited by BQ788 (pA2 7.6), but not by BQ123. 4. Inhibition of Ca2+ channels by nifedipine (0.1 microM) is accompanied by a significant decrease of the maximal response to ET-1 by 40% in the artery and by 30% in the vein. The response of the vein to ET-3 is almost abolished by nifedipine. 5. The results indicate that: (i) endothelins contract the human isolated umbilical artery via stimulation of an ET(A) receptor type; (ii) the contraction induced by ET-1 in the vein is mediated by both ET(A) and ET(B) receptors, while ET-3 stimulates the ET(B) receptor; (iii) the contribution of Ca2+ channels to the contraction mediated by the ET(B) receptor appears to be more important than to that mediated by the ET(A) receptor.
本研究的目的是从药理学角度对人脐血管中存在的内皮素受体进行表征。2. 内皮素-1（ET-1）和内皮素-2（ET-2）对人脐动脉（pEC50分别为7.9和7.5）和脐静脉（pEC50分别为8.1和8.0）均为强效刺激剂。内皮素-3（ET-3）对动脉无活性，但可使静脉收缩（pEC50为7.6）。IRL1620在两种血管中均无活性。激动剂的效价顺序表明，动脉中存在典型的ET(A)受体（ET-1 = ET-2 >> ET-3），而静脉中则是ET(A)和ET(B)受体的混合物（ET-1 = ET-2 > 或 = ET-3）。3. 选择性ET(A)受体拮抗剂BQ123竞争性抑制ET-1对人脐动脉的作用（pA2为6.9），而在静脉中，只有BQ123和BQ788（一种选择性ET(B)拮抗剂）的混合物能使ET-1的累积浓度-反应曲线轻度右移。BQ788可抑制ET-3在静脉中诱导的收缩（pA2为7.6），但BQ123无此作用。4. 硝苯地平（0.1微摩尔）抑制Ca2+通道后，动脉对ET-1的最大反应显著降低40%，静脉中降低30%。硝苯地平几乎完全消除了静脉对ET-3的反应。5. 结果表明：（i）内皮素通过刺激ET(A)型受体使离体人脐动脉收缩；（ii）ET-1在静脉中诱导收缩是由ET(A)和ET(B)受体介导的，而ET-3刺激ET(B)受体；（iii）Ca2+通道对ET(B)受体介导的收缩的贡献似乎比对ET(A)受体介导的收缩更重要。
