Effects of histamine on EGR-1 mRNA expression in astrocytes

• 1、Department of Pharmacology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan 030001

Abstract：AIM: To explore whether histamine can regulate the expression of Egr-1 mRNA in cerebral cortex astrocytes. METHODS: Normal wild-type (WT) mice (n = 4) and histidine decarboxylase knockout (HDC - KO) mice (n = 4) were sacrificed for extracting the total mRNA of the cerebral cortex. Primary cultured rat cortical astrocytes were treated with 10-8, 10-7, 10-6, 10-5 or 10-4 M histamine for 15, 30, 60, 120 or 240 min. H1 receptor antagonist pyrilamine and diphenhydramine and H2 receptor antagonist cimetidine and zolatidine were pretreated for 15 min followed by 10-5 M histamine exposure for 30 min. After histamine treatment, cell total mRNA was extracted. Using real-time quantitative PCR, the expression of Egr-1 mRNA in tissue and cells was tested. RESULTS: Egr-1 mRNA expression in cerebral cortex of HDC - KO mice was significantly lower than that of WT mice. In cultured astrocytes, histamine induced Egr-1 mRNA expression in a dose-and time-dependent manner. The maximum increase in the level of Egr-1 mRNA was produced by a histamine concentration of 10-5 M. In addition, histamine-induced Egr-1 mRNA accumulation peaked at 30 min and declined to the basal level 60 min after commencing stimulation. Furthermore, histamine-induced Egr-1 mRNA expression was inhibited by H1 receptor antagonist pyrilamine and diphenhydramine but not H2 receptor antagonist cimetidine and zolatidine. CONCLUSION: Histamine can upregulate the Egr-1 mRNA expression in cerebral cortex and cultured astrocytes, which may attribute to H1 receptor activation.

Keywords： Pharmacology Histamine Egr-1 Astrocytes