title: Characterization of endothelin receptors in the human umbilical artery and vein.
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.
authors.affiliation: Institute of Pharmacology, University of Ferrara, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bogoni
authors.forename: A
authors.initials: A
authors.lastname: Rizzi
authors.forename: G
authors.initials: G
authors.lastname: Calo
authors.forename: C
authors.initials: C
authors.lastname: Campobasso
authors.forename: P
authors.initials: P
authors.lastname: D'Orleans-Juste
authors.forename: D
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000328:Adult; D001667:Binding, Competitive / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D019333:Endothelin-2 / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011247:Pregnancy; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects*; D014469:Umbilical Arteries / Q000187:drug effects*; D014471:Umbilical Veins / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D019333:Endothelin-2; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; D009543:Nifedipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)