The H3 receptor antagonist clobenpropit protects against Abeta42-induced neurotoxicity in differentiated rat PC12 cells.
The present study was designed to investigate the effect of the H3 antagonist clobenpropit on neurotoxicity induced by Abeta42 in differentiated rat PC12 cells. PC12 cells were exposed to Abeta42 (5 microM) for 24h after clobenpropit applied for 18 h. Cell viability, glutamate release or cell surface expression of NMDA receptors were examined. Pretreatment with clobenpropit ameliorated cell impairment induced by Abeta42. In the presence of Abeta42, clobenpropit increased glutamate release, although there were no differences between the Abeta42-treated sample and control. Meanwhile, in the absence of Abeta42, clobenpropit increased the surface expression of NMDA receptors when the total expression of NMDA receptors was not influenced. These results indicate that one of the mechanisms by which clobenpropit attenuates Abeta42-induced neurotoxicity may act through regulation of glutamate release and NMDA receptor trafficking.
Fu
Qiuli
Q
Department of Pharmacology, Institute of Neuroscience, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Dai
Haibin
H
He
Ping
P
Hu
Weiwei
W
Fan
Yanying
Y
Zhang
Weiping
W
Chen
Zhong
Z
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D018698:Glutamic Acid / Q000378:metabolism; D054828:Histamine H3 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D054828:Histamine H3 Antagonists; D007093:Imidazoles; D009498:Neurotoxins; D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); D018698:Glutamic Acid; D013890:Thiourea; C086108:clobenpropit