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 H-3 antagonist clobenpropit on neurotoxicity induced by A beta 42 in differentiated rat PC-12 cells. PC12 cells were exposed to A beta 42 (5 mu M) 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 A beta 42. In the presence of A beta 42, clobenpropit increased glutamate release, although there were no differences between the A beta 42-treated sample and control. Meanwhile, in the absence of A beta 42, 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 A beta 42-induced neurotoxicity may act through regulation of glutamate release and NMDA receptor trafficking.