Figure 1.

Intracellular activation cascades triggered by histamine receptors (HRs). The pleiotropic effects of histamine are mediated by four histamine receptors: H1R, H2R, H3R, and H4R, which are G protein-coupled receptors. Signaling via H1R leads to activation of intracellular transcription factors, such as PLC (phospholipase C), IP3 (inositol triphosphate), PKC (protein kinase C), DAG (diacylglycerol), and Ca²⁺. H2R signaling acts through activation of adenylyl cyclase (AC), which increases cyclic adenosine monophosphate (cAMP) levels and activates protein kinase A (PKA), while H3R and H4R inhibit this cascade. Those intracellular signaling pathways culminate into protein phosphorylation and transcription of nuclear factor such as nuclear factor kappa B (NF-κB), nuclear factor of activated T-cells (NFAT), cAMP response element binding protein (CREB), and activator protein 1 (AP-1).