Multiple role of histamine H1-receptor-PKC-MAPK signalling pathway in histamine-stimulated nerve growth factor synthesis and secretion.
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.
Lipnik-Stangelj
Metoda
M
Department of Pharmacology and Experimental Toxicology, Faculty of Medicine, Korytkova 2, SI-1000 Ljubljana, Slovenia. metoda.lipnik-stangelj@mf.uni-lj.si
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism*
D009414:Nerve Growth Factors; D011969:Receptors, Histamine H1; D006632:Histamine; D011493:Protein Kinase C