Histamine protects against NMDA‐induced necrosis in cultured cortical neurons through H2 receptor/cyclic AMP/protein kinase A and H3 receptor/GABA release pathways

摘要: Using histamine and the H3 receptor antagonist thioperamide, the roles of histamine receptors in NMDA‐induced necrosis were investigated in rat cultured cortical neurons. Within 3 h of intense NMDA insult, most neurons died by necrosis. Histamine reversed the neurotoxicity in a concentration‐dependent manner and showed peak protection at a concentration of 10−7 m. This protection was antagonized by the H2 receptor antagonists cimetidine and zolantidine but not by the H1 receptor antagonists pyrilamine and diphenhydramine. In addition, the selective H2 receptor agonist amthamine mimicked the protection by histamine. This action was prevented by cimetidine but not by pyrilamine. 8‐Bromo‐cAMP also mimicked the effect of histamine. In contrast, both the adenylyl cyclase inhibitor 9‐(tetrahydro‐2‐furanyl)‐9H‐purine‐6‐amine and the cAMP‐dependent protein kinase inhibitor N‐[2‐(p …