Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors on the human isolated uterine artery

• Published in: British journal of pharmacology Vol. 121; no. 7; pp. 1468 - 1474
• Main Authors: JOVANOVIC, A, JOVANOVIC, S, TULIC, I, GRBOVIC, L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.1997; Nature Publishing
• Subjects: Adult; Antidiuretic Hormone Receptor Antagonists; Biological and medical sciences; endothelium; Female; Genital system. Reproduction; Humans; In Vitro Techniques; Medical sciences; Middle Aged; Oxytocin; Oxytocin - pharmacology; Pharmacology. Drug treatments; Receptors, Oxytocin - physiology; Receptors, Vasopressin - agonists; uterine artery; Uterus - blood supply; Vasoconstriction - drug effects; vasopressin receptors; Human; Partial agonist; Peptide hormone; Smooth muscle; Oxytocic; Neuropeptide; Uterine artery; Muscle contraction; In vitro; Vasopressin; Endothelium; Biological fixation; Uterus; Blood vessel; Female genital system; Neurohypophyseal hormone; Oxytocin(drug); Circulatory system; Mechanism of action; Hormonal receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0701273

The effect of oxytocin on endothelium‐intact and endothelium‐denuded segments of the human uterine artery rings was investigated. In both types of preparation oxytocin induced contraction of human uterine artery with similar potency and efficacy (pEC50 values: 6.95±0.05 vs 7.06±0.01; maximal response values: 61±4.1% vs 63±5.1% for arteries with and without endothelium, respectively). In contrast, human uterine arteries, both intact and denuded of endothelium, did not respond to the addition of the selective oxytocin receptor agonist, [Thr4, Gly7]oxytocin (10 nM–1 μM). The vasopressin receptor antagonists, [d(CH2)5Tyr(Me)]AVP (10–100 nM) and [d(CH2)5,D‐Ile2,Ile4]AVP (300 nM–3 μM) produced parallel rightward shifts of the curves for oxytocin. The Schild plots constrained to a slope of unity gave the following −log KB values: [d(CH2)5Tyr(Me)] AVP vs [d(CH2)5,D‐Ile2,Ile4] AVP 9.24 vs 6.91 and 9.26 vs 6.84 for human uterine artery with intact and those denuded of endothelium, respectively. In contrast, in both types of preparations the oxytocin receptor antagonist, [d(CH2)5Tyr(OMe), 2Orn8]vasotocin (1 μM), did not significantly affect oxytocin‐induced contractions. The calculated pKA values for oxytocin itself also did not differ between preparations: 6.56 and 6.43 for human uterine artery with and without endothelium, respectively. In both types of preparations, the receptor reserve (KA/EC50) was close to unity (intact vs denuded: 3.9 vs 3.0). It is concluded that, in human uterine artery, oxytocin induces contractions that are not modulated by the endothelium. It is likely that oxytocin acts as a partial agonist on human uterine artery, regardless of the endothelial condition. On the basis of differential antagonists affinity and affinity of oxytocin itself, it is probable that receptors involved in oxytocin‐induced contraction in human uterine arteries belong to the V1A vasopressin receptors.