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Biochem Pharmacol. 2006 Nov 30;72(11):1375-81. Epub 2006 Aug 1.

Multiple role of histamine H1-receptor-PKC-MAPK signalling pathway in histamine-stimulated nerve growth factor synthesis and secretion.

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Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, Korytkova 2, SI-1000 Ljubljana, Slovenia.


Histamine is a potent stimulator of nerve growth factor (NGF) production in the central nerve system and in the periphery as well. In this review, the biochemical mechanisms of histamine-stimulated NGF synthesis and secretion, and interactions between histamine, interleukin-1beta, and interleukin-6 are discussed. The main signalling pathway, involved in the stimulation of NGF production by histamine, includes activation of histamine H(1)-receptor, stimulation of Ca(2+)-dependent protein kinase C and mitogen-activated protein kinase. The same signalling pathway is involved in the interactions between histamine, interleukin-1beta, and interleukin-6, where NGF secretion is amplified. Whereas histamine and interleukin-1beta cause additive stimulatory effect on NGF secretion, interaction between histamine and interleukin-6 causes a long-term synergism. Thus, activation of histamine H(1)-receptor-protein kinase C-mitogen-activated protein kinase signalling pathway plays a crucial role not only in the direct stimulation of NGF secretion by histamine, but also in the indirect stimulation via different types of interactions between histamine, interleukin-1beta, and interleukin-6, which may have important therapeutic implications in modulation of NGF production.

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