The Roles of Prostaglandin EP 1 and 3 Receptors in the Control of Human Myometrial Contractility

Abstract

EP3 is the primary receptor subtype that mediates PGE(2) induced contractility in human pregnant myometrium at term and represents a possible therapeutic target.

Responsivity to PGE2 labor induction involves concomitant differential prostaglandin E receptor gene expression in cervix and myometrium

“…However, EP2 and EP4 are classified as relaxant receptors, which couple to G proteins to stimulate adenylate cyclase and induce smooth muscle relaxation by elevating cyclic adenosine monophosphate production (Narumiya et al, 1999;Sugimoto and Narumiya, 2007). Myometrium upregulation of EP3 gene expression described here agree with the results of previous studies reporting that EP3 is likely the primary receptor subtype mediating PGE2-stimulated myometrial contractions (Arulkumaran et al, 2012). These authors concluded that EP3 is likely mainly contractile in its action, remaining on the cell surface and can bind to extracellular exogenous PGE2.…”

“…Because myometrial quiescence is promoted by increased cyclic adenosine monophosphate (Yuan and López-Bernal, 2007), an increase in the expression of genes such as EP3 in the myometrium is expected during physiological parturition, as was observed in our results. This finding has been corroborated by other studies (Arulkumaran et al, 2012), which mainly correlate EP3 with myometrial contractile function.…”

“…Classically, myometrium tissue analyses have found that PGE2 stimulates contractions via EP1 and EP3 receptors, whereas EP2 and EP4 maintain quiescence (Brodt-Eppley and Myatt, 1999). However, few studies have been examined these concepts in detail (Astle et al, 2005;Grigsby et al, 2006a;Arulkumaran et al, 2012;Kandola et al, 2014), and results are inconsistent. This is the first study to observe concomitant and antagonic EP1 and EP3 mRNA expression regulation in the cervical and myometrial tissues in term women with spontaneous labor, indicating differential uterine tissue-regulation during physiological parturition.…”

OBE022, an Oral and Selective Prostaglandin F2α Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor

“…PGE2 has complex dual effects upon the uterus. Acting through EP3, PGE2 mediates contractions (Arulkumaran et al, 2012). PGE2 exerts a relaxatory effect on the uterus through EP2 and EP4 (Kandola et al, 2014).…”

Anti-inflammatory prostaglandins for the prevention of preterm labour

“…PGE 2 and PGF 2a are potent inducers of spontaneous uterine contractility (Crankshaw & Dyal 1994 release via inositol triphosphate and adenylate cyclase and cAMP inhibition respectively (Blanks et al 2007). However, recent data have suggested that spontaneous and PGE 2 -induced myometrial contractility is via the PTGER3 rather than the PTGER1 receptor (Arulkumaran et al 2012). PGF 2a also stimulates myometrial contractility through the FP receptor (PTGFR) likely by increasing intracellular calcium mobilisation (Parkington et al 1999).…”