Roles of Prostaglandin F Synthase

Abstract

Prostaglandin (PG) F₂ is widely distributed in various organs, and exhibits various biological actions such as smooth muscle contraction of uterus [1], bronchus [2], and trachea [3], the initiation of parturition [4], and pain transmission [5]. PGF synthase (PGFS) is a dual function enzyme, which catalyzes the reduction of not only PGD₂ but also PGH₂ on the same molecule [6]. PGFS exhibits reductase activities toward various carbonyl compounds [6], such as phenanthrenequinone (PQ) in addition to PGD₂ and PGH₂. PGFS belongs to the aldo-keto reductase (AKR) superfamily based on substrate specificity, molecular weight, and the amino acid sequence [7–10]. Recently, we isolated the clones of four human enzymes [9,10], including PGFS, which belong to the AKR family. Although the amino acid sequences of these enzymes show high homology (83–98%), only PGFS, which was classified to AKR1 C3 [ 10], catalyzed the reduction of PGD₂ and PGH₂, and the oxidation of 9α, 11β-PGF₂ [9, 10]. Moreover, we developed a high-stringency PCR technique to discriminate fine sequence differences using each specific primer, and examined RT-PCR analysis to estimate expression of AKR mRNAs [10]. The tissue distribution of these four enzymes was different, and human PGFS was localized in lung, liver, kidney, muscle, and peripheral blood lymphocyte. The expression in lymphocytes was markedly suppressed by the T cell mitogen concanavalin A. Moreover, PGFS was abundant in the contractile interstitial cells (CIC) in the alveolar septum of bovine lung, and was diffusely present in the cytoplasm of the endothelial cells of bovine liver. These results suggest that PGFS plays important roles in both the physiological and pathophysiological processes.