Expression Analysis of Prostaglandin E and F Receptors in Rat Uterus, Mesenteric Artery and Uterine Artery for Development of a Surrogate Assay of Uterine Contractility

Abstract

Preterm labor occurs in nearly 10% of U.S. pregnancies and is the leading cause of neonatal morbidity and mortality worldwide. Prostaglandins, specifically of the E and F series, play a key role in myometrial contractility and have been recognized as activators of parturition. As such, modulation of select prostaglandin signaling pathways provides a potential approach to pharmaceutical intervention of preterm labor. Prostaglandin E2 is the most abundantly produced prostanoid and functions through four subtypes of G protein coupled receptors (EP1, EP2, EP3, and EP4). It is generally accepted that EP1 and EP3 serve as pro‐contractility receptors while EP2 and EP4 are relaxatory receptors that promote myometrial quiescence. Prostaglandin F2α (PGF2α) functions through the FP receptor and plays an essential role in uterine contractility during preterm or term labor and delivery. The dynamicity and complexity of prostaglandin pharmacology is an important factor to consider during assay development for the testing of molecules which may not be selective to one receptor subtype.Translational ex vivo assays that enhance throughput of drug candidate screening and decrease the use of experimental animals are increasingly desirable. The objective of this research was to determine the relevance of employing either mesenteric resistance artery or uterine artery segments as surrogate tissues to the uterus in the evaluation of prostaglandin‐induced smooth muscle contraction. The relative expression of EP1, EP2, EP3, EP4, and FP receptor mRNA was determined by RT‐qPCR and compared between the uterine body, uterine artery, and mesenteric artery in the rat. Additionally, the efficacy of PGF2α in eliciting contraction was measured by isometric wire myography and compared between the uterine and mesenteric artery.The results of this study demonstrate that rat mesenteric artery may have utility as a model in the screening of prostaglandin receptor‐targeting molecules. Together, these findings will contribute to the identification of suitable and efficient ex vivo assays by which new pharmacological approaches for the treatment of preterm labor can be evaluated.Support or Funding InformationFerring Research Institute, San Diego, CAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.