Prostanoid receptors in GtoPdb v.2021.2

Prostanoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Prostanoid Receptors [694]) are activated by the endogenous ligands prostaglandins PGD2, PGE1, PGE2 , PGF2α, PGH2, prostacyclin [PGI2] and thromboxane A2. Differences and similarities between human and rodent prostanoid receptor orthologues, and their specific roles in pathophysiologic conditions are reviewed in [448]. Measurement of the potency of PGI2 and thromboxane A2 is hampered by their instability in physiological salt solution; they are often replaced by cicaprost and U46619, respectively, in receptor characterization studies.

Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2 and 5-Hydroxy-PGD2

<p>Biosynthetic crossover of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymatic activities is a productive pathway to convert arachidonic acid into unique eicosanoids. Here we show that COX-2 catalysis with 5-LOX derived 5-hydroxy-eicosatetraenoic acid yields the endoperoxide 5-hydroxy-PGH₂ that spontaneously rearranges to 5-OH-PGE₂ and 5-OH-PGD₂, the 5-hydroxy analogs of arachidonic acid derived PGE₂ and PGD₂. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6<i>E</i>,8<i>E</i>,10<i>E</i>-enoic acid, and by SnCl₂-mediated reduction to 5-OH-PGF₂_a. Both 5-OH-PGE₂ and 5-OH-PGD₂ were unstable and degraded rapidly upon treatment with weak base. The instability hampered detection in biologic samples which was overcome by in situ reduction using NaBH₄ to yield the corresponding stable 5-OH-PGF₂ diastereomers and enabled detection of 5-OH-PGF₂_a in activated primary human leukocytes. 5-OH-PGE₂ and 5-OH-PGD₂ were unable to activate EP and DP prostanoid receptors suggesting their bioactivity is distinct from PGE₂ and PGD₂. </p>

Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2 and 5-Hydroxy-PGD2

<p>Biosynthetic crossover of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymatic activities is a productive pathway to convert arachidonic acid into unique eicosanoids. Here we show that COX-2 catalysis with 5-LOX derived 5-hydroxy-eicosatetraenoic acid yields the endoperoxide 5-hydroxy-PGH₂ that spontaneously rearranges to 5-OH-PGE₂ and 5-OH-PGD₂, the 5-hydroxy analogs of arachidonic acid derived PGE₂ and PGD₂. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6<i>E</i>,8<i>E</i>,10<i>E</i>-enoic acid, and by SnCl₂-mediated reduction to 5-OH-PGF₂_a. Both 5-OH-PGE₂ and 5-OH-PGD₂ were unstable and degraded rapidly upon treatment with weak base. The instability hampered detection in biologic samples which was overcome by in situ reduction using NaBH₄ to yield the corresponding stable 5-OH-PGF₂ diastereomers and enabled detection of 5-OH-PGF₂_a in activated primary human leukocytes. 5-OH-PGE₂ and 5-OH-PGD₂ were unable to activate EP and DP prostanoid receptors suggesting their bioactivity is distinct from PGE₂ and PGD₂. </p>