Histamine protects against NMDA-induced necrosis in cultured cortical neurons through H receptor/cyclic AMP/protein kinase A and H receptor/GABA release pathways.

Abstract

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-bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide reversed the protection by histamine. Thioperamide also attenuated NMDA-induced excitotoxicity, which was reversed by the H3 receptor agonist (R)-alpha-methylhistamine but not by pyrilamine and cimetidine. In addition, the protection by thioperamide was inhibited by the GABA(A) receptor antagonists picrotoxin and bicuculline. Further study demonstrated that the protection by thioperamide was due to increased GABA release in NMDA-stimulated samples. These results indicate that not only the H2 receptor/cAMP/cAMP-dependent protein kinase pathway but also the H3 receptor/GABA release pathway can attenuate NMDA-induced neurotoxicity.

• Authors: Haibin Dai, Zhongmiao Zhang, Yongpin Zhu, Yao Shen, Weiwei Hu, Yuwen Huang, Jianhong Luo, Henk Timmerman, Rob Leurs, Zhong Chen
• Journal: Journal of neurochemistry (J Neurochem) Vol. 96 Issue 5 Pg. 1390-400 (Mar 2006) ISSN: 0022-3042 [Print] England
• PMID: 16478529 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Excitatory Amino Acid Agonists
• GABA Antagonists
• Histamine Agonists
• Histamine Antagonists
• Receptors, Histamine
• Picrotoxin
• 8-Bromo Cyclic Adenosine Monophosphate
• gamma-Aminobutyric Acid
• N-Methylaspartate
• Histamine
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases
• Bicuculline

Topics

• 8-Bromo Cyclic Adenosine Monophosphate (pharmacology)
• Animals
• Animals, Newborn
• Apoptosis (drug effects, physiology)
• Bicuculline (pharmacology)
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Cerebellar Cortex (cytology)
• Cyclic AMP (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Dose-Response Relationship, Drug
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Excitatory Amino Acid Agonists (toxicity)
• GABA Antagonists (pharmacology)
• Histamine (pharmacology)
• Histamine Agonists (pharmacology)
• Histamine Antagonists (pharmacology)
• N-Methylaspartate (toxicity)
• Necrosis (chemically induced, prevention & control)
• Neurons (drug effects, pathology)
• Picrotoxin (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Histamine (physiology)
• Time Factors
• gamma-Aminobutyric Acid (metabolism)