[3H]Histamine uptake and release by astrocytes from rat brain: Effects of sodium deprivation, high potassium, and potassium channel blockers

Abstract

Histamine transport has been characterized in cultured astroglial cells of rat brain. The kinetics of [3H]-histamine uptake yielded a Km of 0.19 +/- 0.03 microM and a Vmax of 3.12 +/- 0.75 pmol X mg protein-1 X min-1. Transport system revealed high affinity for histamine and an approximately ten times higher capacity than that shown in cultured glial cells of chick embryonic brain. Ouabain which interferes with utilization of ATP to generate ion gradients, and the replacement of Na+ with choline inhibited the initial rate of uptake showing a strong Na(+)-dependency and suggesting the presence of a tightly coupled sodium/histamine symporter. Dissipation of K(+)-gradient (in > out) by high K+ or by K(+)-channel blockers, BaCl2, (100 microM), quinine (100 microM) or Sparteine (20 microM) produced also remarkable inhibitions in the uptake of [3H]-histamine. Impromidine, a structural histamine-analogue could inhibit the uptake non-competitively in a range of concentrations of 1 to 10 microM with a Ki value of 2.8 microM, indicating the specificity of the uptake. [3H]histamine uptake measurements carried out by using a suspension of dissociated hypothalamic cells, of rat brain showed a strong gliotoxin-sensitivity and yielded a Km of 0.33 +/- 0.08 microM; and a Vmax of 2.65 +/- 0.35 pmoles x mg protein-1 x min-1. The uptake could be reversed by incubating the cells in histamine-free Krebs medium. The [3H]histamine efflux was sensitive to Na+ omission, ouabain treatment and high K+ or K+ channel blockers, resulting in marked elevations in the efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for bidirectional histamine transport by murine hematopoietic progenitor cells

“…Yet, we could demonstrate that they do not inhibit histamine uptake via Ha receptor blockade [13]. It was therefore plausible that hematopoietic progenitor cells possessed a means of histamine transport, as described for a few other cell types such as astrocytes, endothelial and glial cells [16][17][18].…”

“…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].…”

“…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.…”

Mercury-stimulated histamine uptake and binding in cultured astroglial and cerebral endothelial cells

“…A histamine uptake mechanism has been identified in chicken and rat cerebral astrocytes and also in cerebral endothelial cells on the basis of experiments in which virtually homogeneous cell cultures were incubated with the radiolabeled amine (Huszti et al 1990(Huszti et al , 1994Huszti and Balogh, 1995). The initial rate of histamine uptake reflecting a high affinity interaction that could be described by Michaelis-Menten kinetics, required external Na 1 and was inhibited by histamine analogues (2-methylhistamine, 4-methylhistamine, impromidine), desmethylimipramine and depolarizing agents (barium chloride and sparteine) but also by heavy metals (Pb 11 and Hg 11 ) in low 1-10 µM concentrations.…”

Binding of histamine H3‐receptor antagonists to hematopoietic progenitor cells

“…This take up is temperature-dependent and requires sodium exchange for optimal function. It was observed in astrocytes, endothelial and glial cells [7][8][9].…”