Evidence for bidirectional histamine transport by murine hematopoietic progenitor cells

Abstract

Murine hematopoietic progenitor cells synthesize substantial amounts of histamine in response to IL-3 or calcium ionophore. They also take up extracellular histamine by an active transport system. In the present study we demonstrate that this system mediates both influx and efflux of histamine. Indeed, MR16155 and thioperamide, the two 1-13 antagonists which are most effective in inhibiting histamine uptake, likewise diminish the release of preloaded histamine from bone marrow cells. These compounds also inhibit the release of histamine which has been newly synthesized by hematopoietic progenitors in response to IL-3 or calcium ionophore, as assessed by the accumulation of the mediator inside the cells in the presence of the antagonists. The potency of different histamine receptor antagonists as inhihitors of histamine release increases with their capacity to block histamine uptake.Key words: Hematopoietic progenitor; Histamine; Bidirectional transport; Interleukin-3 Histamine uptake is temperature-dependent and partially requires sodium exchange [13]. Although we have provided evidence that this phenomenon is not mediated by classical histamine receptors, Ha receptor antagonists, such as thioperamide and MR16155, are potent inhibitors. Conversely to the polyamine transport system, which exists in numerous cell types and has been extensively studied [14,15], histamine transport seems to be restricted to astrocytes, endothelial and glial cells, and is still poorly understood [16][17][18]. It has been suggested that astrocytes could use the same means of transport for histamine uptake and release [18]. Herein, we provide evidence for a bidirectional transporter in bone marrow cells (BMC) and in the IL-3-dependent cell line FDCP1, as assessed by the finding that the inhibitors of histamine uptake likewise decrease release of preloaded histamine. We also show that this system is involved in the release of endogenous histamine which is newly synthesized in response to IL-3 or calcium ionophore since we found a decrease in histamine release accompanied by an increase in intracellular histamine contents in the presence of H3 receptor antagonists.

Corticosterone-Sensitive Monoamine Transport in the Rat Dorsomedial Hypothalamus: Potential Role for Organic Cation Transporter 3 in Stress-Induced Modulation of Monoaminergic Neurotransmission

“…Other mediators of DMH histamine uptake may include the newly described plasma membrane monoamine transporter (Engel et al, 2004), which is relatively insensitive to corticosterone (K i ϭ 450 M) and the H3 histamine receptor (Corbel and Dy, 1996). In contrast to its effect on histamine uptake, corticosterone was less efficacious at inhibiting MPP ϩ uptake than was D22 (Fig.…”

Evidence for the Presence of Histamine Uptake into the Synaptosomes of Rat Brain

“…Huszti et al [8][9][10] showed that histamine uptake by astroglial and cerebral endothelial cells represented a carrier-mediated, energy-and sodium-dependent highaffinity mechanism, which was definitely involved in the inactivation and clearance of neuronal histamine. It was also established that hematopoietic progenitor cells from murine bone marrow had the capacity to take up considerable amounts of extracellular histamine, which accumulated inside the cells [2] . This histamine transport is partially dependent on the presence of an electrochemical Na + gradient such as astrocytes and endothelial cells [8][9][10] and it is temperature-dependent as well.…”

“…This histamine transport is partially dependent on the presence of an electrochemical Na + gradient such as astrocytes and endothelial cells [8][9][10] and it is temperature-dependent as well. The hematopoietic progenitors also possessed a histamine transport system with bidirectional functions, the inward and outward currents [2] . Recently, we reported that the characteristics of [ 3 H]histamine uptake into bone marrowderived cells from L -histidine decarboxylase gene knockout mice [17] .…”

Binding of histamine H3‐receptor antagonists to hematopoietic progenitor cells

“…As shown in Fig. 2 bi-directional [14], we examined whether the compounds that blocked histamine uptake also inhibited its release from IL-3-induced BMC. We found that in the presence of iodoproxyfan, carboperamide, FUB 181 or FUB 130 at optimal concentration (10 \iM), bone marrow supernatants contained about 60% less histamine than controls (Fig.…”

“…the blockade of histamine uptake also inhibits the release of newly synthesized, IL-3-induced histamine from BMC, while intracellular histamine levels increase. II-3-dependent cell lines composed of immature myeloid cells arrested at a particular stage of the differentiation scheme have a similar transport system [14].…”