Why PGD₂ has different functions from PGE₂

Abstract

Prostaglandin (PG) D2 and PGE2 are positional isomers; however, they sometimes exhibit opposite physiological functions, such as in cancer development. Because DP receptors are considered to be a duplicated copy of EP2 receptors, PGD2 and PGE2 cross‐react with both receptors. These prostanoids may act as biased agonists for each receptor. In reviewing this field, a hypothesis was proposed to explain the opposed effects of these prostanoids from the viewpoints of the evolution of, mutations in, and biased activities of their receptors. Previous findings showing more mutations/variations in DP receptors than EP2 receptors among individuals worldwide indicate that DP receptors are still in a rapid evolutionary stage. The opposing effects of these prostanoids on cancer development may be attributed to the biased activity of PGE2 for DP receptors, which may incidentally develop during the process of the old ligand, PGE2 gaining selectivity to newly diverged DP receptors.

Identification and Imaging of Prostaglandin Isomers Utilizing MS3 Product Ions and Silver Cationization

“…For example, the positional isomers PGE 2 and PGD 2 both play crucial roles in inflammation. Recently, it has been argued that PGE 2 and PGD 2 exhibit opposing effects due to biased activities of their receptors, and it has been shown that their individual abundances can affect the severity of the disease . Additional studies have demonstrated the opposing effects of PGE 2 and PGD 2 in regulation of food intake, body temperature, sleep, and ischemic injury. − Thus, to understand their individual role in biological systems, it is crucial to analytically identify the individual isomeric species.…”