Glucagon effects on 3H-histamine uptake by the isolated guinea-pig heart during anaphylaxis.

Mirko Rosic,Suzana Pantovic,Vladimir Jakovljevic,Vladimir Zivkovic,Oberdan Parodi,Maja Colic,Vuk Jokovic

doi:10.1155/2014/782709

Mirko Rosic, Suzana Pantovic + Show 5 more

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https://doi.org/10.1155/2014/782709

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Abstract

We estimated the influence of acute glucagon applications on 3H-histamine uptake by the isolated guinea-pig heart, during a single 3H-histamine passage through the coronary circulation, before and during anaphylaxis, and the influence of glucagon on level of histamine, NO, O2 −, and H2O2 in the venous effluent during anaphylaxis. Before anaphylaxis, glucagon pretreatment does not change 3H-histamine Umax and the level of endogenous histamine. At the same time, in the presence of glucagon, 3H-histamine Unet is increased and backflux is decreased when compared to the corresponding values in the absence of glucagon. During anaphylaxis, in the presence of glucagon, the values of 3H-histamine Umax and Unet are significantly higher and backflux is significantly lower in the presence of glucagon when compared to the corresponding values in the absence of glucagon. The level of endogenous histamine during anaphylaxis in the presence of glucagon (6.9–7.38 × 10−8 μM) is significantly lower than the histamine level in the absence of glucagon (10.35–10.45 × 10−8 μM). Glucagon pretreatment leads to a significant increase in NO release (5.69 nmol/mL) in comparison with the period before glucagon administration (2.49 nmol/mL). Then, in the presence of glucagon, O2 − level fails to increase during anaphylaxis. Also, our results show no significant differences in H2O2 levels before, during, and after anaphylaxis in the presence of glucagon, but these values are significantly lower than the corresponding values in the absence of glucagon. In conclusion, our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis.

Highlights

Anaphylaxis is a serious allergic reaction in which specific antigens provoke a sudden release of mast cell-derived and basophil-derived mediators of allergic phenomena including histamine, platelet-activating factor, leukotrienes, prostaglandins, tryptase, serotonin, cytokines, and nitric oxide (NO) [1,2,3,4,5]
Our results show that glucagon increases NO release and prevents the increased release of free radicals during anaphylaxis, and decreases histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the heart during anaphylaxis
In this study we have shown that glucagon increased NO release and prevented the increased release of free radicals during anaphylaxis, and decreased histamine level in the venous effluent during cardiac anaphylaxis, which may be a consequence of decreased histamine release and/or intensified histamine capturing by the cells in the heart during anaphylaxis

Summary

Introduction

Anaphylaxis is a serious allergic reaction in which specific antigens provoke a sudden release of mast cell-derived and basophil-derived mediators of allergic phenomena including histamine, platelet-activating factor, leukotrienes, prostaglandins, tryptase, serotonin, cytokines, and nitric oxide (NO) [1,2,3,4,5]. Released histamine plays a main role in genesis of most functional changes occurring in the anaphylaxis [3] This biogenic amine exists within the mast cells and basophilic leukocytes, but it could be released by endothelial cells, aggregating platelets, lymphocytes, and monocytes/macrophages as well as enterochromaffin-like cells and histamine neurons [9,10,11]. Histamine enhances the expression of adhesion molecules in vascular endothelial cells, thereby augmenting leukocyte-endothelial cell interactions, an important event in atherogenesis [24] This biogenic amine suppresses hepatic LDL receptor expression and reduces plasma HDL cholesterol in rats [25]. Kounis reported that any substances which protect mast cell surface and stabilize mast cell membrane could appear as a new therapeutic way capable of preventing acute coronary and acute cerebrovascular events

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