Prostanoid GPCR Assays

Overview of Prostanoid Receptors

Prostaglandins (PGs) mainly include PGD₂, PGI₂, PGE₂, PGF_2α and thromboxane A₂ (TXA₂). After synthesis, PGs need to be transported into the extracellular microenvironment through specific proteins. Prostaglandins function by binding to some specific receptors, which are the PGD receptor (DP), the four PGE receptors (EP₁, EP₂, EP₃, and EP₄), the PGF receptor (FP), the PGI receptor (IP), and the TXA receptor (TP). Several studies have revealed that PG receptor signaling is involved in various pathological regulations.

Fig.1 Signal transduction by G_s-coupled prostanoid receptors. (Hirata, 2011)

Vital Roles of Prostanoid Receptors

Prostaglandin receptors have different tissue distributions and roles. For example, DP receptors are expressed in the small intestine, stomach, and uterus. DP₁ is implicated in platelet activation and sleep regulation, and DP₂ is closely related to immune cell activation. EP receptors (EP_1-4) are comprised of different prostaglandin receptors. EP receptors play important roles in regulating smooth muscle behavior. FP receptors are involved in the breakdown of the corpus luteum. IP receptors are important cardiovascular regulators.

Primary Mechanisms

The DP₁-EP₂-EP₄-IP subfamily affects the cAMP signaling pathway. Coupled with G_s, these receptors activate AC, resulting in the conversion of ATP to cAMP.

Receptor	Gene	Mechanism	Agonists	Antagonists
EP1 Receptor	PTGER1	EP1 receptor is a Gq-coupled receptor.	Misoprostol Sulprostone	AH 6809 ONO 8130 SC 19220 SC 51089 SC 51322
EP2 Receptor	PTGER2	EP2 receptor is coupled to the Gαs signaling pathway. EP2 receptor signals via the cAMP pathway.	OMDI	AH 6809 PF 04418948 TG 4-155
EP3 Receptor	PTGER3	EP3 Receptor is a Gi-coupled receptor.	Sulprostone	DG 041 L-798,106
EP4 Receptor	PTGER4	EP2 receptor is coupled to the Gαs signaling pathway. EP2 receptor activates the cAMP pathway.	TCS 2510	BGC 20-1531 hydrochloride ER 819762 GW 627368 L-161,982 ONO AE3 208
TP Receptor	TBXA2R	TP receptors can be coupled to both Gαq and Gαi.	U 46619	S 18886
FP Receptor	PTGFR	FP receptors commonly activate the Gαq signal transduction pathway.	ONO-9054	AL-8810 AL-3138
IP Receptor	PTGIR	IP receptors couple to Gαs proteins to stimulate the PKC pathway.	Beraprost sodium Epoprostenol Iloprost Selexipag Treprostinil	BAY-u 3405 Ro 1138452 hydrochloride
DP Receptor	PTGDR	DP receptors are coupled to Gαs.	AL-6598	AMG 853 BAY-u 3405

Assay List of Prostanoid Receptors

Creative Biolabs can provide a range of assays of prostanoid receptors. You can choose the assay in the list or contact us for more information:

Published Data

Paper Title	The affinity, intrinsic activity and selectivity of a structurally novel EP2 receptor agonist at human prostanoid receptors
Journal	British journal of pharmacology
Published	2019
Abstract	The simple non-prostaglandin EP2 receptor agonists identified in this study are the focus of a lead optimization program driven by medicinal chemistry. Evaluation of compounds against specific cells and tissues is a critical point in the screening process to ensure proper optimization of agonist efficacy. The program led to the identification of several potential development candidates. The EP2 receptor agonist PGN-9856 emerged as a potential candidate for preclinical development based on chemical structure considerations. PGN-9856 exhibits multiple activities, and in addition to tocolysis and ocular hypotension, its broad potential as a modulator of inflammation also attracts extensive attention.
Result	PGN-9856 was shown to be a high-affinity ligand for human recombinant EP2 receptors. In addition to high-affinity binding, PGN-9856 has also been proven to be a potent and complete EP2 receptor agonist with a high level of selectivity for EP1, EP3, EP4, DP, FP, IP, and TP receptors. Furthermore, in cells overexpressing the human recombinant EP2 receptor, PGN-9856 exhibited comparable effects to the endogenous agonist PGE2. Notably, PGN-9856 has no apparent affinity for various other receptors, ion channels, and enzymes. Importantly, PGN-9856 exhibited tocolytic, anti-inflammatory, and long-acting intraocular pressure-lowering properties, which are consistent with its potent EP2 receptor agonist properties. Fig.2 Agonist potency of PGN-9856, PGN-9858, PGN-9862, PGN-9863 and PGE2 at human recombinant EP2 receptors. (Coleman, 2019)

References

1. Hirata, T.; Narumiya, S. Prostanoid receptors. Chemical reviews. 2011; 111(10): 6209-6230.
2. Coleman, R.A.; et al. The affinity, intrinsic activity and selectivity of a structurally novel EP2 receptor agonist at human prostanoid receptors. British journal of pharmacology. 2019; 176(5): 687-698.