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Histamine-neurotrophin-3 interactions in cultured rat astrocytes


Neurotrophin-3 (NT-3) is produced by astrocytes, in addition to neurons, and monoamine neurotransmitters play a role in controlling NT-3 synthesis [1]. The impact of histamine on the regulation of NT-3 synthesis in cultured astrocytes has not been studied in detail. Therefore, we focused our present study on the active involvement of multiple histaminergic receptor and intracellular mechanisms in the regulation of NT-3 production by histamine.


Histamine (1 μM) significantly and transiently elevates NT-3 mRNA levels by 2.2-fold after 30 min of incubation following by 2.1-fold increase in NT-3 intracellular levels after 6 h. Its stimulation was partly inhibited by the H1 antagonists triprolidine and mepyramine, the H2 antagonists famotidin and cimetidin, and by the H3 antagonist ciproxifan. NT-3 levels in astrocytes were increased by specific and selective H1, H2 and H3 agonists, but none of the tested agonists was able to reach the level of histamine's stimulatory effect. Different activators of basic intracellular histamine receptor second messenger systems (forskolin, dibutyryl cAMP, dBcAMP; as well as calcimycin, i.e. Ca2+ ionophore A23187) and phorbol 12-myristate 13-acetate, TPA) markedly increase the cellular level of NT-3 protein. Histamine-induced cellular levels of NT-3 were significantly reduced by H-89 (an inhibitor of protein kinase A, PKA) and by staurosporin (an inhibitor of protein kinase C, PKC). Studying histamine receptor subtype expression in astrocytes using quantitative RT-PCR we confirmed that the expression levels of histamine H1 and H2 receptors (already shown in radioligand binding) as well as of H3 receptors are high.


Our study confirmed that the synthesis of NT-3 in astrocytes is regulated by the histaminergic system and indicate the possible involvement of multiple, complex histamine H1, H2 and H3 receptors and corresponding intracellular mechanisms involving the cAMP/PKA pathway, as well as mobilisation of Ca2+ ions and activation of PKC.


  1. Mele T, Čarman-Kržan M, Jurič DM: Regulatory role of monoamine neurotransmitters in astrocytic NT-3 synthesis. Int J Devel Neurosci.

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Correspondence to Marija Čarman-Kržan.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mele, T., Jurič, D.M. & Čarman-Kržan, M. Histamine-neurotrophin-3 interactions in cultured rat astrocytes. BMC Pharmacol 9 (Suppl 2), A61 (2009).

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