Carrier-mediated uptake and release of histamine by cultured rat cerebral endothelial cells

Huszti, Z.; Deli, Mária A.; Joó, Ferenc

doi:10.1016/0304-3940(94)11202-t

Cited by 20 publications

(12 citation statements)

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“…We have shown that HA was taken up into cultured cerebral endothelial cells and this uptake had similar properties to that seen in astroglial cultures [13]. The kinetic parameters (K M = 0.3 mM; V max = 4.6 pmol/mg protein/min) and the sensitivity to the uptake inhibitors/stimulators of HA were comparable to those obtained with cultured astroglial cells [7][8][9].…”

Section: Histamine Uptake Into Cerebral Endothelial Cellssupporting

confidence: 48%

Histamine uptake into non-neuronal brain cells

Huszti¹

2003

Inflammation Research

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IntroductionThe main function of various transport systems is to maintain the cellular concentrations of the physiological substances. However, transport also contributes to various mechanisms in clearing and scavenging substances from the interstitial spaces. In the CNS, the termination of many neurotransmitters involves rapid removal from the synapse; mainly by uptake either into presynaptic terminal or into the surrounding glia through specialised transport systems.Histamine (HA) is a regulator of the vascular permeability through cerebrovascular endothelium as well as being a central neurotransmitter. However, no neuronal uptake of HA has been detected in vertebrates [1]. In invertebrates, HA is taken up into the photoreceptor terminals and surrounding glia and replenishes HA stores by an activitydependent fashion [2]. In mammalian neurones, a polyspecific cation transporter (hOCT 2 ) can transport HA along with monoamines [3] but as it shows a low affinity for HA (K M in mM range), it is not assumed to play a considerable role in HA inactivation.Besides inactivation, the possibility of a clearance mechanism in which glial and cerebral endothelial HA uptake are co-operatively involved, has also been considered. We have focused our research on HA uptake by CNS-resident nonneuronal cells (including mast cells) bearing physiological significance. Histamine uptake by astroglial cellsAstrocytes perform a variety of CNS functions, including uptake of a number of neurotransmitters. In 1985, we showed that HA is taken up and slowly metabolised by chick astroglial cells [4]. In chick astroglial cells (grown as monolayer culture), uptake was found to be saturable, with high affinity for HA and relatively low capacity (K M = 0.24 mM; V max = 0.31 pmol/mg protein/min), showing energy-requirements and strong sensitivity to extracellular Na + concentration. The uptake vs [Na + ] curve was saturable, fitted the Michaelis-Menten equation and resulted in a K M of 172 mM for Na + . HA taken up into these cells was slowly metabolised and/or released ('reversed uptake'), dependent on the shift of the Na + /K + gradient [5].Bidirectonal uptake could also be detected in astroglial cultures from postnatal (P 0 -P 6 ) rat brains with similar affinity for HA (K M = 0.19 mM) but with 10 times higher capacity (V max = 3.12 pmol/mg protein/min) [6]. It was noteworthy that partial dissipations of the inward oriented Na + (in < out) and the outward oriented K + (in > out) gradient could reverse the inward-directed HA uptake resulting in a carrier-mediated release of HA. The release of HA was increased by high [K + ] and K + channel blockers which might depolarise the cells, suggesting an electrogenic transporter for the uptake. The HA analogues, 2-meHA and 4-me-HA showed significant inhibition while well-known uptake inhibitors (imipramine and cocaine) did not show much effect on the uptake [6]. Impromidine and the impromidine derivative, VUF 8407 [9] showed potent inhibitory effects on HA uptake and antagonistic actions on the H 3 auto-r...

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Section: Histamine Uptake Into Cerebral Endothelial Cellssupporting

confidence: 48%

Histamine uptake into non-neuronal brain cells

Huszti¹

2003

Inflammation Research

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“…Since Na+ is neccessary for the uptake of histamine in both glial and endothelial cells, (Huszti et al 1990(Huszti et al , 1994(Huszti et al & 1995 and the Na+ gradient is maintained almost exclusively by the Na+/K+ pump in these cells, the inhibitory effect of Pb++ on (Na+/Kf) ATP-ase (Chandra et al 1984) might result in the decreased rate of histamine uptake. Since Na+ is neccessary for the uptake of histamine in both glial and endothelial cells, (Huszti et al 1990(Huszti et al , 1994(Huszti et al & 1995 and the Na+ gradient is maintained almost exclusively by the Na+/K+ pump in these cells, the inhibitory effect of Pb++ on (Na+/Kf) ATP-ase (Chandra et al 1984) might result in the decreased rate of histamine uptake.…”

Section: Discussionmentioning

confidence: 99%

“…Both uptakes revealed high affinity for the transporter and strong Na+-dependency (Huszti et al 1990(Huszti et al , 1995. Both uptakes revealed high affinity for the transporter and strong Na+-dependency (Huszti et al 1990(Huszti et al , 1995.…”

Section: Comparison Of Pb+ +And Hg++ Effects On [3h]-histamine Uptakementioning

confidence: 94%

Effects of Lead and Mercury on Histamine Uptake by Glial and Endothelial Cells

Huszti

Balogh

1995

Pharmacology & Toxicology

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The effects of lead and mercury on [3H]-histamine uptake by cultured astroglial and endothelial cells of rat brain were studied. Experimental data showed that both metal ions inhibited the uptake in both cell types of concentrations as low as 1-10 microM. The effects were consistent with non/competitive inhibitions. With either lead or mercury exposure, the inhibition of the uptake was greater in astroglial than in cerebral endothelial cells. Contrary to the above findings, 100 microM of mercuric chloride produced stimulation of histamine uptake and this stimulation was much more pronounced in cultured cerebral endothelial cells than in astroglial cells. Inhibition of [3H]-histamine uptake by lead acetate and mercuric chloride was considered to be association with a loss of the transmembrane Na+ and/or K+ gradient while stimulation of the uptake by high concentration of mercury might be related to a direct effect on histamine transporter. It is noteworthy, that cultured astroglial cells, derived from neonatal rat brain, are much more sensitive to the toxic effects of these heavy metal ions than cultured endothelial cells derived from the brain capillaries of the same species of animals.

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“…Although there is evidence to suggest neuronal and non-neuronal uptake [1,2] as a part of the histamine inactivation pathway, no specifi c histamine transporter has been identifi ed or cloned yet. Histamine uptake has been shown to occur via other transporters, including organic cation transporter 2 (OCT2) [3,4] into neurons, or extraneuronal monoamine transporter into nonneuronal cells [5,6].…”

Section: Introductionmentioning

confidence: 99%

Histamine transport in neonatal and adult astrocytes

Kržan

Schwartz²

2006

Inflamm. res.

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IntroductionAs a neurotransmitter, histamine should be synthesized, stored in vesicles, released upon neuronal stimulation and inactivated afterwards. Although there is evidence to suggest neuronal and non-neuronal uptake [1, 2] as a part of the histamine inactivation pathway, no specifi c histamine transporter has been identifi ed or cloned yet. Histamine uptake has been shown to occur via other transporters, including organic cation transporter 2 (OCT2) [3,4] into neurons, or extraneuronal monoamine transporter into nonneuronal cells [5,6]. Since astrocytes are located perisynaptically and have transporters for removing other neurotransmitters [7], we wanted to elucidate whether histamine is transported into cultured astrocytes. Therefore, in this study we examined the characteristics and the time-course of histamine uptake in type 1 astrocytes prepared from neonatal and adult rat cortex. Materials and methodsAstrocyte and shake-off cell cultures: These were prepared from cortices of 3-days old and adult (220-250 g) Sprague-Dawley rats of both sexes and cultured as previously described [8]. The composition of cultures was determined immunohistochemically using the following primary antibodies: anti-GFAP (1:1000) to detect astrocytes; anti OX-42 (1:200) to detect microglia; anti-galactocerebroside (1:200) to detect oligodendrocytes; anti-A2B5 (1:200) to detect progenitor cells and corresponding secondary antibodies. After forming a complex with avidin-biotin-peroxidase, cells were developed in diaminobenzidine-tetrahydrochloride, washed, mounted and coverslipped.Histamine uptake: Monolayer cultures were preincubated with uptake buffer (25 mM HEPES, 125 mM NaCl, 4.8 mM KCl, 1.2 mM KH 2 PO4 4 , 1.2 mM MgSO 4 , 1.7 mM CaCl 2 and 5.6 mM glucose, pH 7.4 for 30 min at 37°C (total uptake) and 4°C (non-specifi c uptake). Histamine transport was initiated by addition of 3 H-histamine (fi nal conc. 0.2 µM). After 20 minutes the reaction was stopped by placing the dishes into an ice-water bath. Cells were lysed with 0.5 M NaOH, radioactivity measured and protein concentration determined using Bio-Rad method.To determine the effect of Na + on histamine uptake, NaCl in the uptake buffer was replaced with choline chloride. Na + K + ATP-ase was inhibited by adding 1 mM ouabain. Results and discussionAstrocyte cultures prepared either from neonatal or adult rat cortices contained 95-100 % type 1 astrocytes, showing positive GFAP and negative A2B5 immunostaining. The composition of shake-off cells from neonatal rats was 32 % microglia, 27 % O2A progenitors, 40 % type 2 astrocytes, and 1 % oligodendrocytes, while the cultures from adult cortex consisted of 36 % microglia, 15 % progenitors, 31 % type 2 astrocytes and 18 % oligodendrocytes.Histamine uptake was measured in neonatal and adult cultured astrocytes over the time period from one to fi ve weeks after the last subculture. Histamine uptake was already evident at one week in both neonatal and adult astrocyte cultures, but signifi cant Na + -dependence and ouabain-sensitivity...

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Carrier-mediated uptake and release of histamine by cultured rat cerebral endothelial cells

Cited by 20 publications

References 17 publications

Histamine uptake into non-neuronal brain cells

Histamine uptake into non-neuronal brain cells

Effects of Lead and Mercury on Histamine Uptake by Glial and Endothelial Cells

Histamine transport in neonatal and adult astrocytes

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