title: Low pH enhances 2-aminoethoxydiphenyl borate-induced cell death of PC12 cells.
abstract: 2-Aminoethoxydiphenyl borate (2-APB) is widely used as a pharmacological tool for analysis of cellular Ca(2+) regulation. In this study, we found that external acid potentiated neural cell death induced by 2-APB in rat pheochromocytoma 12 (PC12) cells. 2-APB induced cell death in half of the PC12 cells within 30min at pH 6.6 but not at pH 7.4. The extent of the 2-APB-induced cell death increased in a dose-, time- and pH-dependent manner. Ca(2+)-imaging revealed that 2-APB increased [Ca(2+)](i) in PC12 cells at pH 6.6. Removal of extracellular Ca(2+) and chelation of intracellular Ca(2+) inhibited the 2-APB-induced cell death. Antagonists of the store-operated Ca(2+) (SOC) channel (SKF96365 and ruthenium red) blocked both 2-APB-induced cell death and Ca(2+) influx, but those for transient receptor potential channels (BCTC, TRIM and BTP2), acid-sensing ion channels (amiloride) and proton-sensing G-protein-coupled receptors (U73122) did not. These results suggest that 2-APB induces neural cell death via Ca(2+) overload through SOC channel activation under acidic pH.
authors.affiliation: Department of Veterinary Pharmacology, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohta
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival; D006863:Hydrogen-Ion Concentration; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D012964:Sodium / Q000378:metabolism
chemical_list: D001896:Boron Compounds; D002121:Calcium Channel Blockers; D043562:Receptors, G-Protein-Coupled; D012964:Sodium; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium