Histamine, Metabolic Remodelling and Angiogenesis: A Systems Level Approach

Abstract

Histamine is a highly pleiotropic biogenic amine involved in key physiological processes including neurotransmission, immune response, nutrition, and cell growth and differentiation. Its effects, sometimes contradictory, are mediated by at least four different G-protein coupled receptors, which expression and signalling pathways are tissue-specific. Histamine metabolism conforms a very complex network that connect many metabolic processes important for homeostasis, including nitrogen and energy metabolism. This review brings together and analyses the current information on the relationships of the "histamine system" with other important metabolic modules in human physiology, aiming to bridge current information gaps. In this regard, the molecular characterization of the role of histamine in the modulation of angiogenesis-mediated processes, such as cancer, makes a promising research field for future biomedical advances.

Keywords: angiogenesis; metabolic remodelling; systems biology.

Figure 1

Relationships between histamine and other amines with different physiological and cellular processes. The processes are depicted in green boxes. Abbreviations (by alphabetical order): Aas, amino acids; Arg/Orn, arginine/ornithine; CA, catecholamines; E-PLP, pyridoxal phosphate dependent enzyme; GABA, gamma aminobutyric acid; H1R, histamine receptor 1; H2R, histamine receptor 2; H3R, histamine receptor 3; H4R, histamine receptor 4; Hia, histamine; His, histidine; NMDAR, N-Methyl-D-aspartic acid receptor; NO, nitric oxide; PAs, polyamines; ROS, reactive oxygen species; SAM, S-adenosyl methionine; Sert, serotonin.

Figure 2

Network of signaling interactions between the histamine receptors and the genes involved in reprogramming cancer metabolism. Abbreviations used as in Table 2.