Pharmacological potential of biogenic amine–polyamine interactions beyond neurotransmission

Abstract

Histamine, serotonin and dopamine are biogenic amines involved in intercellular communication with multiple effects on human pathophysiology. They are products of two highly homologous enzymes, histidine decarboxylase and L-aromatic amino acid decarboxylase, and transmit their signals through different receptors and signal transduction mechanisms. Polyamines derived from ornithine (putrescine, spermidine and spermine) are mainly involved in intracellular effects related to cell proliferation and death mechanisms. This review summarizes structural and functional evidence for interactions between components of all these amine metabolic and signalling networks (decarboxylases, transporters, oxidases, receptors etc.) at cellular and tissue levels, distinct from nervous and neuroendocrine systems, where the crosstalk among these amine-related components can also have important pathophysiological consequences. The discussion highlights aspects that could help to predict and discuss the effects of intervention strategies. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 Abbreviations CYP, cytochrome P450; DAO, diamine oxidase; DDC, dopamine decarboxylase; DFMO, difluoromethyl ornithine; HDC, histidine decarboxylase; MATE1, multidrug and toxin extrusion transporter-1; ODC, ornithine decarboxylase; SAM, S-adenosyl methionine; sVMATs, vesicular monoamine transporters The aim of the present reviewIntegration of biological information can reveal new properties and features that could contribute to progress in the characterization of complex systems; this is a fundamental principle of systems biology (Kitano, 2002). A human being can be considered as a system composed of different subsystems specialized in certain functions: interchange with the environment, defence, internal coordination (metabolic homeostasis, motor and cognitive capacities) and reproduction.Biogenic amines and polyamines have relevant roles in all of these human functions, but the topic is too extensive to be the subject of a single review. Excellent reviews have been published recently on the pharmacological potential of biogenic amines (and related compounds) in neurotransmission (Nuutinen and Panula, 2010;Lin et al., 2011;Lodge and Grace, 2011;Sharp and Cowen, 2011;Tiligada et al., 2011;Deneris and Wyler, 2012;Fleck et al., 2012; and others within this volume).In the present work, we focus our attention on a set of small physiological subsystems beyond neurotransmission, where components related to cationic amino acids, dopamine and serotonin are present and can interact ( Figure 1). Here, we also discuss the potential consequences of these metabolic connections for pharmacology, as well as pointing out some important gaps of information that require further basic research in order to generate useful translational information. General biochemical and physiological features of biogenic amines and polyaminesBiogenic amines ...

Preventing H2O2-induced toxicity in primary cerebellar granule neurons via activating the PI3-K/Akt/GSK3β pathway by kukoamine from Lycii Cortex

“…In fact, the polyamine backbones, mainly spermine, spermidine, and putrescine, are ubiquitous cellular components playing particularly important roles in defence of injury for the central nervous system (Adibhatla, Hatcher, Sailor, & Dempsey, 2002;Sánchez-Jiménez, Ruiz-Pérez, Urdiales, & Medina, 2012). Previous studies have indicated that exogenous polyamines and their derivatives are effective in curing neurotrauma, like mechanical injuries, neurotoxins, and cerebrovascular mal- Fig.…”

Aminas biogénicas: un ejemplo de “poder” del metabolismo “secundario” de mamíferos

“…Sin embargo, aún quedan muchas lagunas de información sobre las cadenas de acontecimientos moleculares implicados en cada caso. Descifrar del modo más completo posible la red de interacciones que se establecen en cada tipo celular, y entre ellos, es fundamental para poder intervenir en la larga lista de patologías en las que las aminas están implicadas (8,9). Desde hace más de una década reclamamos la necesidad de hacer un esfuerzo de investigación colaborativa y multidisciplinar que incluya el apoyo de recursos biocomputacionales de valor predictivo y la posterior validación experimental de las predicciones (1,3,4,8-11).…”

Histamine pharmacology: four years on

“…Intra-and intercellular crosstalk among histamine and amine-related components has important pathophysiological consequences, as reviewed in detail by Sánchez-Jiménez et al (2013). Histamine and the immune system have a long history, with the H1 and H2 receptors much studied as key players.…”