Effects of TEI-3356, a stable analogue of prostacyclin, on the neurite outgrowth in mouse neuroblastoma Neuro-2a cells and the learning and memory impairments in β-amyloid protein-infused rats

• Published in: Japanese Journal of Pharmacology Vol. 82; no. suppl.1; p. 183
• Main Authors: Takami Arai, Katsutoshi Sakurai, Yumiko Yamada, Jun Suzuki, Yorimasa Suwa
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 2000
• ISSN: 0021-5198

Previous studies showed that some types of prostaglandins (PGs) were capable of promoting the neurite outgrowth in neuronal cells and, among of them, PGE_1 had the most potent activity. In the present study, we found that TEI-3356 [(16S)-15-deoxy-16-hydroxy-16-methyl-9(O)-methano-⊿^6 (9α)-prostaglandin I_1 ], a stable analogue of prostacyclin, promoted the neurite outgrowth in mouse neuroblastoma Neuro-2a cells, and its activity was at least ten times higher than that of PGE_1 . Although TEI-3356 was known to be a highly selective agonist for EP3, one of the PG receptors, we speculated that its neurite outgrowth promoting-activity was not mediated by this receptor, since the. (16R)-isomer of TEI-3356, which had almost no affinity for EP3, also showed an effect on the neurites to the same extent as TEI-3356. In in vivo study, we also found that TEI-3356 ameliorated the learning and memory impairments induced by the continuous intra-cerebroventricular infusion of β-amyloid protein (1-42) in rats when used at a remarkably low dose. These findings suggest that TEI-3356 and/or its derivatives could be a candidate for novel anti-dementia drugs.