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Prostaglandins play important roles in the gastric mucosal protection and gastric ulcer healing. Administration of the prostaglandin derivatives has been proven to be effective for both treatment and prevention of gastric ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs). The risk of postoperative hemorrhage following gastric endoscopic submucosal dissection (ESD) is higher in patients with antithrombotic therapy. Mucosal protective agents, including prostaglandin derivatives, may be effective in preventing post-ESD hemorrhage in patients on antithrombotic therapy. Recently, NSAIDs-induced small intestinal damages are recognized by video capsule endoscopy and balloon endoscopy. Prostaglandin derivatives are also useful for these small intestinal damages.

A large number of compounds have been reported to prevent ischemia-induced neuronal death, whereas there are few described to enhance recovery of brain functions. Since neurotrophins do not only prevent neuronal death but also protect neuronal circuits, they may be potential candidates. However, their poor penetration of the blood-brain-barrier hampers their development as therapeutic agents. In this context, low-molecular-weight compounds that possess neurite outgrowth- and neuronal survival-promoting activities may be alternative candidates. Neurite outgrowth-promoting prostaglandins, which were recently-synthesized based on the chemical structure of anti-tumor cyclopentenone prostaglandin derivatives, have been characterized by their neurotrophic effects on neurons in the central nervous system. In this paper, we present a review of these compounds as therapeutic agents against several neurodegenerative diseases.

Prostanoid receptors are the G-protein-coupled, rhodopsin-type receptors with seven transmembrane domains and consist of eight types and subtypes. Although the overall homology is not high, there are several regions specifically conserved among them. These regions are considered to form the ligand binding pocket for the structures common to prostanoid molecules, and the other regions to confer specificity for ligand binding. The PGI and PGD receptors have relatively high homology (40%) at the amino acid level and share the same signalling pathway. To determine which structural domains of these receptors confer ligand binding specificity, we constructed a series of chimeric receptors from the mouse PGI and PGD receptors. These chimeric receptors were expressed in COS-7 cells, and their abilities to bind prostaglandins and their analogues were examined. The region from the sixth transmembrane domain to the carboxyl terminus of the PGI receptor was first replaced by the corresponding region of the PGD receptor. This chimeric receptor binds both PGD2 and PGE2, though the ability to bind iloprost, a PGI receptor agonist, and PGE1 does not change. This result indicates that the sixth and seventh transmembrane domains of the PGI receptor play an important role in distinction of structural difference between PGE1 and PGE2 in the alpha-side chain. These binding characteristics did not change when the region up to the third transmembrane domain of the PGI receptor was replaced with the corresponding region of the PGD receptor. However, when the first extracellular loop including a portion of the second transmembrane domain was further replaced, the abilities to bind PGE1, PGE2 and iloprost were eliminated. This result indicates that this domain of the PGD receptor is responsible for distinction of structural differences between PGD2 and PGE2 on the cyclopentane ring.