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

Huszti, Z.; Madar�sz, E.; Schlett, Katalin; Jo�, F.; Szab�, A.; Deli, Mária A.

doi:10.1002/(sici)1097-4547(19970401)48:1<71::aid-jnr7>3.0.co;2-b

Cited by 7 publications

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References 13 publications

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“…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]. Similarly, the uptake process required energy and following OGD or iodoacetate treatment of 3 and 6 min incubation periods, there was 15 -75 % and 67 % inhibition respectively (Fig.…”

Section: Histamine Uptake Into Cerebral Endothelial Cellssupporting

confidence: 73%

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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: 73%

“…We observed that mercuric salts, added in distinct (25 -200 mM) concentrations to the incubation medium, exerted marked (1.5 -3.0 fold) enhancements in HA uptake [7]. From our previous and present findings [8], we extended our studies to Zn 2+ , the virtually non-toxic IIB cation.…”

Section: Histamine Uptake By Astroglial Cellssupporting

confidence: 64%

Histamine uptake into non-neuronal brain cells

Huszti¹

2003

Inflammation Research

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“…(2) Huszti et al, 1997 Stimulation of histamine uptake and binding by mercuric compounds (2) Note. CNS, central nervous system; GLUT1, glucose transporter-1; LAT1, large neutral amino acid tansporter; L-DOPA, L-3,4-dihydroxyphenylalanine; MCT1, monocarboxylic acid transporter; OAT, organic anion transporter; OCT, organic cation transporter; OCTN2, organic cation transporter/carnitine transporter; TAUT, taurine transporter.…”

Section: Octn2mentioning

confidence: 99%

Rat Brain Endothelial Cell Lines for the Study of Blood–Brain Barrier Permeability and Transport Functions

2005

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(1) In vitro models of the BBB have been developed from cocultures between bovine, porcine, rodent or human brain capillary endothelial cells with rodent or human astrocytes. Since most in vivo BBB studies have been performed with small laboratory animals, especially rats, it is important to establish a rat brain endothelial (RBE) cell culture system that will allow correlations between in vitro and in vivo results. The present review will constitute a brief description of the best characterized RBE cell lines (RBE4, GP8/3.9, GPNT, RBEC1, TR-BBBs and rBCEC4 cell lines) and will summarize their recent and important contribution to our current knowledge of the BBB transport functions and permeability to blood-borne solutes, drugs, and cells. (2) In most cases, primary cultures of RBE cells were transduced with an immortalizing gene (SV40 or polyoma virus large T-antigen or adenovirus E1A), either by transfection of plasmid DNA or by infection using retroviral vectors. In one case however, the conditionally immortalized TR-BBB cell line was derived from primary cultures of brain endothelial cells of SV40-T-expressing transgenic rats. (3) All cell lines appear to have an endothelial morphology. The absence of foci formation would mean that the cells are not transformed. The endothelial origin is shown by the expression of Factor VIII-related antigen. Immortalized RBE cells express all the enzymes and transporters that are considered as specific for the blood-brain barrier endothelium, with similar characteristics to those expected from in vivo analyses, but at a significantly lower level. Some RBE cell lines are responsive to astroglial factors, such as RBE4 cells, rBEC4, and TR-BBB cells. None of the immortalized RBE cell lines appear to generate the necessary restrictive paracellular barrier properties that would allow to use them in transendothelial permeability screening. (4) RBE cell lines have been used to demonstrate that transporters such as organic cation transporter/carnitine transporter, serotonin transporter, and the ATA2 system A isoform are expressed in rat brain endothelium. When the transporter is shown to be expressed with the same properties in the immortalized RBE cells as in vivo, regulation studies may be initiated even if the transporter is down-regulated. Pharmacological applications have been proposed with well-characterized transporters such as monocarboxylic acid transporter-1, large neutral amino acid tansporter-1, nucleoside carrier systems, and P-glycoprotein. RBE cell monolayers have also been used to investigate the mechanism of the transendothelial transport of large molecules, such as immunoliposomes or nanoparticles, potentially useful as drug delivery vectors to the brain. (5) RBE4 and GP8 cell lines have been extensively used to demonstrate that intercellular adhesion molecule-1 (ICAM-1) engagement in brain endothelial cells triggers multiple signal transduction pathways. Using functional assays, it was established that ICAM-1 signaling is intimately and actively involved in facili...

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“…A more unique characteristic of glial HA uptake, one which exhibits a distinct specificity for the transport carrier, is its marked promotion by mercurials at 25-500 µM (Huszti et al, 1997a). The enhanced uptake is similar to that established for the basic uptake in term of its inhibition by uptake blocking agents (e.g., impromidine) and sensitivity toward sulfhydryl compounds; mercuryinduced increase in HA uptake is completely reversed by 1 mM dithiotreitol or by 0.1 mM cysteamine, strongly suggesting sulfhydryl-mercury interactions in this process ( Fig.…”

Section: Characteristics Of the Uptakementioning

confidence: 53%

“…Although HA appears to be a high affinity ligand for glial HA uptake carrier, its low abundance relative to HA receptors presents difficulties in purifying and reconstituting the carrier. The differential effects of mercuric salts on carrier and receptor(s) protein (Huszti et al, 1997a) might offer a promising strategy for purification and reconstitution of glial HA carrier.…”

Section: Discussionmentioning

confidence: 99%

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

Cited by 7 publications

References 13 publications

Histamine uptake into non-neuronal brain cells

Histamine uptake into non-neuronal brain cells

Rat Brain Endothelial Cell Lines for the Study of Blood–Brain Barrier Permeability and Transport Functions

Carrier‐mediated high affinity uptake system for histamine in astroglial and cerebral endothelial cells

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