Signaling pathways in histamine receptors. Histamine can mediate its functions via its 4 G-protein-coupled H1R to H4R. Rac and RhoA activation is mediated by H1R via Gq binding to PLC stimulation. Moreover, H2R controls both c-Fos and c-Jun expression by distinct signaling pathways such as protein kinase C (PKC) and p70 S6 kinases, respectively. The H3R could activate AKT, PLA2, PLA, and MAPK pathways, and H4R stimulates MAPK and PLC pathways. H1R indicates histamine H1 receptor; MAPK, mitogen-activated protein kinase; PLA indicates phospholipase A; PLC, phospholipase C.