title: DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.
abstract: Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. hezhi2003@126.com.cn
authors.forename: Zhi
authors.initials: Z
authors.lastname: He
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Xulin
authors.initials: X
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Jianguo
authors.initials: J
authors.lastname: Chen
authors.forename: Lianjun
authors.initials: L
authors.lastname: Guo
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000172:deficiency*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000473:pathology*; D000860:Hypoxia / Q000150:complications*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats
chemical_list: D018696:Neuroprotective Agents; D010627:Phenethylamines; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane; D018698:Glutamic Acid; D011189:Potassium Chloride; D007770:L-Lactate Dehydrogenase; D005947:Glucose; D002118:Calcium