The H₃ receptor antagonist clobenpropit protects against Aβ42-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 Aβ42 in differentiated rat PC12 cells. PC12 cells were exposed to Aβ42 (5 μM) for 24 h 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 Aβ42. In the pres-ence of Aβ42, clobenpropit increased glutamate release, although there were no differences between the Aβ42-treated sample and control. Meanwhile, in the absence of Aβ42, 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 Aβ42-induced neurotoxicity may act through regulation of glutamate release and NMDA receptor trafficking.