Resolvin D2 and Resolvin D1 Differentially Activate Protein Kinases to Counter-Regulate Histamine-Induced [Ca2+]i Increase and Mucin Secretion in Conjunctival Goblet Cells

Resolvin (Rv) D2 and RvD1 are biosynthesized from docosahexaenoic acid (DHA) and promote resolution of inflammation in multiple organs and tissues, including the conjunctiva. Histamine is a mediator produced by mast cells in the conjunctiva during the allergic response. We determined the interaction of RvD2 with histamine and its receptor subtypes in cultured conjunctival goblet cells and compared them with RvD1 by measuring intracellular [Ca2+] and mucous secretion. Treatment with RvD2 significantly blocked the histamine-induced [Ca2+]i increase as well as secretion. RvD2 and RvD1 counter-regulate different histamine receptor subtypes. RvD2 inhibited the increase in [Ca2+]i induced by the activation of H1, H3, or H4 receptors, whereas RvD1 inhibited H1 and H3 receptors. RvD2 and RvD1 also activate distinct receptor-specific protein kinases to counter-regulate the histamine receptors, probably by phosphorylation. Thus, our data suggest that the counter-regulation of H receptor subtypes by RvD2 and RvD1 to inhibit mucin secretion are separately regulated.

The Roles of Cardiovascular H2-Histamine Receptors Under Normal and Pathophysiological Conditions

This review addresses pharmacological, structural and functional relationships among H2-histamine receptors and H1-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H2-histamine-receptors in cardiac diseases will be examined. The use of H2-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H2-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H2-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H2-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H2-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H2-histamine receptors in cardiac disease and whether cardiomyocyte specific H2-histamine receptor agonists and antagonists should be developed.

Analysis of association between histamine receptor gene HRH1, HRH2, HRH3, HRH4 polymorphisms and asthma in children

Asthma is a common multifactorial disease characterized by chronic inflammation of the respiratory tract. Insufficient control of asthma symptoms significantly reduces the patient’s quality of life, leads to the risk for more severe disease and disability. It is important to research the role of gene polymorphisms encoding proteins involved in various stages of histamine metabolism, which is one of the known mediators of allergic reactions.The aim of the study was to investigate histamine receptor gene polymorphisms (HRH1, HRH2, HRH3, HRH4) in children with asthma and the control group.Methods. The study of HRH1 (rs901865), HRH2 (rs2067474), HRH3 (rs3787429), HRH4 (rs11665084) gene polymorphisms in asthma patients and healthy individuals aged 2 - 17 years of different ethnicities living in the Republic of Bashkortostan was carried out. Genotyping of polymorphisms was performed by polymerase chain reaction with fluorescence detection.Results. In Tatars, rs901865*CT genotype and rs901865*T allele of HRH1 gene were associated with asthma development and decrease in spirometry measures (MEF25). In Tatars, a statistically significant model of the interaction between HRH1 (rs901865), HRH3 (rs3787429), and HRH4 (rs11665084) gene polymorphisms that leads to the risk of asthma was established.Conclusion. The results of this study reveal certain aspects of asthma pathogenesis and suggest the possible involvement of polymorphic variants of histamine receptors genes HRH1, HRH3, HRH4 in the development of asthma.

Activity-dependent circuitry plasticity via the regulation of the histamine receptor level in the Drosophila visual system

Activity-dependent synaptic plasticity is crucial for responses to the environment. Although the plasticity mechanisms of presynaptic photoreceptor neurons in the Drosophila visual system have been well studied, postsynaptic modifications remain elusive. In addition, further studies on the adaption of the visual system to different light experiences at a circuitry scale are required. Using the modified transcriptional reporter of intracellular Ca2+ method, we describe a way to visualize circuitry changes according to different light experiences. We found enhanced postsynaptic neuronal activity responses in lamina monopolar neuron L2 after prolonged light treatment. Although L1 also has connections with photoreceptors, there were no enhanced activity responses in L1. We also report in this study that activity-dependent transcriptional downregulation of inhibitory histamine receptors (HRs) occurs in postsynaptic neuron L2, but not in L1, during continuous light conditions. We expressed exogenous HR proteins in L2 neurons and found that it attenuated the enhanced activity response caused by constant light exposure. These findings, together with the fact that histamine is the main inhibitory neurotransmitter released by photoreceptors in the Drosophila visual system, confirmed our hypothesis that the activity-dependent transcriptional downregulation of HRs is responsible for the constant light exposure-induced circuitry response changes in L2. The results successfully demonstrated the selective circuit change after synaptic remodeling evoked by long-term activation and provided in vivo evidence of circuitry plasticity upon long-term environmental stimulation.

PEDIATRIC MASTOCYTOSIS: AN UPDATE

Mastocytosis is a rare clonal disorder, characterized by excessive proliferation and accumulation of mast cells (MC) in various organs and tissues. Cutaneous mastocytosis (CM), the most common form in children, is defined when MC infiltration is limited to the skin. Systemic mastocytosis (SM), the most common form in adults, is characterized by MC proliferation and accumulation in organs, such as bone marrow, lymph nodes, liver and spleen (1). Genetic aberrations, mainly the KIT D816V mutation, play a crucial role in the pathogenesis of mastocytosis, resulting in enhancing MC survival and subsequent accumulation in organs and tissues (2,3). CM includes 3 forms: solitary mastocytoma, maculopapular cutaneous mastocytosis (MPCM) and diffuse cutaneous mastocytosis (DCM). In the majority of children with CM, skin lesions regress spontaneously around puberty; unfortunately, in a few cases, it is not a self-limiting disease (4). Even if SM occurs occasionally, all children with mastocytosis require planned follow-up over time. Children with mastocytosis often suffer from MC mediator-related symptoms, the most common of which is itching, often triggered by rubbing the lesions. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers. Treatment with H1 and H2 histamine receptor blockers on demand, and the availability of epinephrine auto-injectors for the patients to use in case of severe anaphylactic reactions are recommended.