title: The involvement of P2X₁ receptor in pyramidal cell degeneration in the rat hippocampus after trimethyltin administration.
abstract: The P2 family of receptors for adenosine 5'-triphosphate (ATP) is involved in several neuronal and glial cell functions in the central nervous system (CNS), and impaired function of these receptors is associated with both neuronal and glial dysfunction. Using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis, we examined the expression profiles of P2 subtype receptors in the rat hippocampus following treatment with the neurotoxicant trimethyltin (TMT). Among the subtypes, P2X₁ exhibited a unique profile, with an increase in expression prior to the onset of cell death after TMT administration, and a gradual decrease thereafter in neuronal cells in the rat hippocampus. This expression pattern was similar to that of cyclooxygenase-2 (COX-2) following TMT administration. The P2X₁ antagonist NF499 strongly prevented neuronal cell death induced by TMT in the CA1 region, and successfully suppressed locomotor hyperreactivity. Furthermore, NF449 administration also inhibited COX-2 expression in the CA1 region on day 3 following TMT treatment, whereas no change was observed in the CA3. These findings suggest that P2X₁ plays a primary role in TMT-induced neuronal cell death in the CA1 region.
authors.affiliation: Drug Discovery Research, Drug Safety Research Labs, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shirakawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakano
authors.forename: Naomi
authors.initials: N
authors.lastname: Hachiya
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Kato
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D058474:Receptors, Purinergic P2X1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014298:Trimethyltin Compounds / Q000633:toxicity
chemical_list: D058474:Receptors, Purinergic P2X1; D014298:Trimethyltin Compounds; C046488:trimethyltin