Effect of oxytocin as a partial agonist at vasoconstrictor vasopressin receptors on the human isolated uterine artery
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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 (pEC 50 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, [Thr 4, Gly 7]oxytocin (10 n M–1 μ M). The vasopressin receptor antagonists, [d(CH 2)5 Tyr(Me)]AVP (10–100 n M) and [d(CH 2)5,D‐Ile 2,Ile 4]AVP (300 n M–3 μ M) 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(CH 2)5 Tyr(Me)] AVP vs [d(CH 2)5,D‐Ile 2,Ile 4] 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(CH 2)5 Tyr(OMe), 2 Orn 8]vasotocin (1 μ M), did not significantly affect oxytocin‐induced contractions. The calculated p KA 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/EC 50) 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 V 1A vasopressin receptors.
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Oxytocin given at much higher doses to prevent post-partum haemorrhage appears to act not by oxytocin receptors but by V1a receptors on the uterine artery.
“Oxytocin is given at much higher doses to prevent post‐partum haemorrhage 59, but this action appears to be mediated not by oxytocin receptors but by V1a receptors on the uterine artery 60.”
From Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers (2016) · cites this paper as [60]
Oxytocin is known to induce uterine contractions.
“Although oxytocin is known to induce uterine contractions,57”
From Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial (2016) · cites this paper as [57]
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Measuring Oxytocin and Vasopressin: Bioassays, Immunoassays and Random Numbers
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“Oxytocin is given at much higher doses to prevent post-partum haemorrhage (59), but this action appears to be mediated not by oxytocin receptors but by V1a receptors on the uterine artery (60).”
BackgroundOxytocin and its receptors are synthesized in the rat vasculature
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- Authors
- Jovanović, A., Jovanović, S., Tulić, I., & Grbović, L.
- Affiliations
- University of Belgrade (RS)
- Corresponding author
- Jovanović, Aleksandar
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1997-07
- Volume
- 121
- Issue
- 7
- Pages
- 1468-1474
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1564832
- OpenAlex
- W1990822250
- Cited by
- 17
- References
- 42
- Citations by year
- 2021: 1 · 2016: 3 · 2012: 1
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- oxytocin, vasopressin receptor, uterine contraction, endothelium, vasopressin receptor antagonists, oxytocin receptor antagonist, arginine vasotocin, receptor reserve, receptor binding affinity, pEC50, Schild analysis, d(CH2)5Tyr(Me)AVP, vasopressin
- MeSH terms
- Adult, Female, Humans, Middle Aged, Oxytocin, Uterus, Vasoconstriction, Receptors, Vasopressin, Receptors, Oxytocin, Antidiuretic Hormone Receptor Antagonists, In Vitro Techniques
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