Contractility measurements of human uterine smooth muscle to aid drug development

Arrowsmith, Sarah, Keov, Peter, Muttenthaler, Markus and Gruber, Christian W. (2018) Contractility measurements of human uterine smooth muscle to aid drug development. Journal of Visualized Experiments, 2018 131: . doi:10.3791/56639

Author Arrowsmith, Sarah
Keov, Peter
Muttenthaler, Markus
Gruber, Christian W.
Title Contractility measurements of human uterine smooth muscle to aid drug development
Journal name Journal of Visualized Experiments   Check publisher's open access policy
ISSN 1940-087X
Publication date 2018-01-26
Year available 2018
Sub-type Article (original research)
DOI 10.3791/56639
Open Access Status Not yet assessed
Volume 2018
Issue 131
Total pages 12
Place of publication CAMBRIDGE
Publisher Journal of Visualized Experiments
Language eng
Abstract Discovery and characterization of novel pharmaceutical compounds or biochemical probes rely on robust and physiologically relevant assay systems. We describe methods to measure ex vivo myometrium contractility. This assay can be used to investigate factors and molecules involved in the modulation of myometrial contraction and to determine their excitatory or inhibitory actions, and hence their therapeutic potential in vivo. Biopsies are obtained from women undergoing cesarean section delivery with informed consent. Fine strips of myometrium are dissected, clipped and attached to a force transducer within 1 mL organ baths superfused with physiological saline solution at 37 °C. Strips develop spontaneous contractions within 2–3 h under set tension and remain stable for many hours (>6 h). Strips can also be stimulated to contract such as by the endogenous hormones, oxytocin and vasopressin, which cause concentration-dependent modulation of contraction frequency, force and duration, to more closely resemble contractions in labor. Hence, the effect of known and novel drug leads can be tested on spontaneous and agonist-induced contractions. This protocol specifically details how this assay can be used to determine the potency of known and novel agents by measuring their effects on various parameters of human myometrial contraction. We use the oxytocin- and V receptor antagonists, atosiban and SR49059 as examples of known compounds which inhibit oxytocin- and vasopressin-induced contractions, and demonstrate how this method can be used to complement and validate pharmacological data obtained from cell-based assays to aid drug development. The effects of novel agonists in comparison to oxytocin and vasopressin can also be characterized. Whilst we use the example of the oxytocin/vasopressin system, this method can also be used to study other receptors and ion channels that play a role in uterine contraction and relaxation to advance the understanding of human uterine physiology and pathophysiology.
Keyword Contraction
Drug discovery
Human uterus
Issue 131
Organ bath
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID I 3243
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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Created: Fri, 09 Feb 2018, 02:39:02 EST