Characterization of endothelin receptors in the human umbilical artery and vein

Br J Pharmacol. 1996 Dec;119(8):1600-4. doi: 10.1111/j.1476-5381.1996.tb16078.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Binding, Competitive / drug effects
  • Calcium Channel Blockers / pharmacology
  • Endothelin Receptor Antagonists
  • Endothelin-1 / metabolism
  • Endothelin-1 / pharmacology
  • Endothelin-2 / metabolism
  • Endothelin-2 / pharmacology
  • Female
  • Humans
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Nifedipine / pharmacology
  • Peptides, Cyclic / pharmacology
  • Pregnancy
  • Receptors, Endothelin / agonists
  • Receptors, Endothelin / drug effects*
  • Umbilical Arteries / drug effects*
  • Umbilical Veins / drug effects*

Substances

  • Calcium Channel Blockers
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelin-2
  • Peptides, Cyclic
  • Receptors, Endothelin
  • Nifedipine
  • cyclo(Trp-Asp-Pro-Val-Leu)