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K Andreas

Publications and source records attributed to K Andreas.

At least 19 recordsLinked to original sources
PubMed2000

Non-N-methyl-D-aspartate (NMDA) receptor antagonist 1,2,3, 4-tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulphonamide (NBQX) decreases functional disorders in cytotoxic brain oedema.

N-methyl-D-aspartate (NMDA) and non-NMDA receptors were found to be involved in development of functional disorders caused by hexachlorophene. In order to specify the role of glutamate receptors we studied the protective effects of the selective antagonist of the kainate/(+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor/channel 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulphonamide disodium (NBQX) and of the non-competitive NMDA receptor antagonist ifenprodil tartrate on coordinative motor behaviour of adult male Wistar rats as assessed in a simple 'ladder-test'. Neurotoxic injury of the cerebrum after hexachlorophene administration and putative amelioration after treatment with test substances was demonstrated histologically. Hexachlorophene-induced motor disturbance remitted spontaneously when stopping the noxis, but remittance occurred significantly earlier when NBQX [0.45 and 0.6 mg/kg intraperitoneal (i.p.)] was applied as well. Ifenprodil (0.15 to 1.2 mg/kg) did not improve the motor function. Vacuolation of white matter of the whole cerebrum was observed after 3 weeks of treatment with hexachlorophene. These morphological alterations caused by hexachlorophene treatment [central nervous system (CNS) vacuolation] spontaneously revert only after 5-6 weeks. The 5-day duration with test substances was too short for remission of vacuolation which thus may not apply to the situation after treatment with glutamate antagonists, despite improvement of motor function. The results suggest that kainate/AMPA receptor channels are at least partially involved in the mechanism of brain damage induced by hexachlorophene, however, the polyamine binding site of the NMDA receptor evidently is not involved.

Animals↗
PubMed1999

Voltage-sensitive Ca2+ channels, intracellular Ca2+ stores and Ca2+-release-activated Ca2+ channels contribute to the ATP-induced [Ca2+]i increase in differentiated neuroblastoma x glioma NG 108-15 cells.

Activation of ionotropic P2X7 purinoreceptors in NG108-15 cells directly opens non-selective cation channels, leading to an increase in intracellular Ca2+ concentration ([Ca2+]i) and membrane depolarization and, hence, by indirect opening of voltage-stimulated Ca2+ channels (VSCC) to further increases of [Ca2+]i, whereas activation of the metabotropic P2Y receptor causes intracellular Ca2+ release. The quantitative contribution of Ca2+ entry and release to ATP-induced [Ca2+]i increase in differentiated NG108-15 cells is not known. Here we have investigated the Ca2+ influx and Ca2+ release components by studying [Ca2+]i in Fura-2-loaded cells and by using the following tools: nifedipine to block L-type VSCC, omega-conotoxin GVIa (omegaCT) to block N-type VSCC and thapsigargin to deplete intracellular Ca2+ stores. With 1.8 mM Ca2+ in the medium, ATP (600 microM) increased [Ca2+]i by 656 +/- 50 nM (n = 11). This response was reduced to 72% by nifedipine (50 microM), to 63% by omegaCT (1 microM), and to 31% by nifedipine and omegaCT in combination. Since nifedipine and omegaCT completely block VSCC in our model, the remaining 31% of [Ca2+]i increase could be caused by influx via P2X7-activated non-selective channels or by intracellular release mediated by P2Y receptors. When Ca2+-free medium was used to exclude Ca2+ influx, ATP (600 microM) increased [Ca2+]i by only 34 +/- 4 nM (n = 4), indicating that the majority of [Ca2+]i increase depends on Ca2+ influx. A similar rise by 37 +/- 4 nM (n = 4) was observed with the selective P2Y agonist UTP (150 microM). This small response was sensitive to thapsigargin and hence represents Ca2+ release. The remainder (i.e. total [Ca2+]i increase minus nifedipine-, omegaCT- and thapsigargin-sensitive [Ca2+]i increases) should, therefore, represent Ca2+ influx via P2X7 non-selective cation channels.

Adenosine Triphosphate↗
PubMed1999

The effects of verapamil and diltiazem on N-, P- and Q-type calcium channels mediating dopamine release in rat striatum.

1. The putative inhibitory effects of verapamil and diltiazem on neuronal non-L-type Ca2+ channels were studied by investigating their effects on either K+- or veratridine-evoked [3H]-dopamine ([3H]-DA) release in rat striatal slices. Involvement of N-, P- and Q-type channels was identified by sensitivity of [3H]-DA release to omega-conotoxin GVIA (omega-CTx-GVIA), omega-agatoxin IVA (omega-Aga-IVA) and omega-conotoxin MVIIC (omega-CTx-MVIIC), respectively. 2. KCl (50 mM)-evoked [3H]-DA release was abolished in the absence of Ca2+, and was insensitive to dihydropyridines (up to 30 microM). It was significantly blocked by omega-CTx-GVIA (1 microM), omega-Aga-IVA (30 nM) and was confirmed to be abolished by omega-CTx-MVIIC (3 microM), indicating involvement of N-, P- and Q-type channel subtypes. 3. Verapamil and diltiazem inhibited K+-evoked [3H]-DA release in a concentration-dependent manner. The inhibitory effects of verapamil or diltiazem (each 30 microM) were fully additive to the effect of omega-CTx-GVIA (1 microM), whereas co-application with omega-Aga-IVA (30 nM) produced similar effects to those of omega-Aga-IVA alone. 4. As shown previously, veratridine-evoked [3H]-DA release in Ca2+ containing medium exclusively involves Q-type Ca2+ channels. Here, diltiazem (30 microM) did not inhibit veratridine-evoked [3H]-DA release, whereas verapamil (30 microM) partially inhibited it, indicating possible involvement of Q-type channels in verapamil-induced inhibition. However, verapamil (30 microM) inhibited this release even in the absence of extracellular Ca2+, suggesting that Na+ rather than Q-type Ca2+ channels are involved. 5. Taken together, our results suggest that verapamil can block P- and at higher concentrations possibly N- and Q-type Ca2+ channels linked to [3H]-DA release, whereas diltiazem appears to block P-type Ca2+ channels only.

Animals↗
PubMed1999

Nicardipine inhibits N-type calcium channels in dbcAMP-differentiated neuroblastoma x glioma hybrid cells (NG 108-15 cells).

AIM: To investigate the possibility of dihydropyridine inhibition of N-type calcium channels. METHODS: Effects of nifedipine and nicardipine on the high K(+)-induced intracellular Ca2+ concentration ([Ca2+]i) increase were studied by measuring [Ca2+]i using the fluorescent indicator Fura-2. RESULTS: Pretreatment of cells with nifedipine 50 mumol.L-1 inhibited the high K(+)-induced [Ca2+]i transient by about 60% (n = 3); however, pretreatment of cells with nicardipine 10 mumol.L-1 completely prevented the high K(+)-evoked [Ca2+]i increase in dibutyryl cyclic AMP (dbcAMP)-differentiated NG 108-15 cells (n = 5). The high K(+)-induced [Ca2+]i increase was mediated by L- and N-type voltage-sensitive calcium channels (VSCC) in NG 108-15 cells. CONCLUSION: Nicardipine at micromolar range inhibited both L- and N-type VSCC in dbcAMP-differentiated NG 108-15 cells whereas nifedipine mainly inhibited L-type calcium channels.

Bucladesine↗
PubMed1998

Different potencies of dihydropyridine derivatives in blocking T-type but not L-type Ca2+ channels in neuroblastoma-glioma hybrid cells.

Evidence has accumulated that classic L-type Ca2+ channel blockers with a dihydropyridine structure also inhibit T-type Ca2+ channels in certain types of central and peripheral neurons and in smooth muscle cells, albeit with a lower potency. Thus beneficial therapeutic effects of dihydropyridines in cardiovascular and neurological diseases may not only be associated with L-type but also with T-type Ca2+ channel blockade. Little is known about the exact order of potency of dihydropyridine derivatives at T-type Ca2+ channels. Here we investigate the efficacy and potency of four therapeutically used compounds, i.e. nifedipine, nimodipine, nicardipine, niguldipine, in the neuroblastoma-glioma cell line NG108-15. For comparative purposes the Ca2+ channel agonist Bay K 8644 was included. Ca2+ channel currents were measured with the whole-cell voltage clamp technique. Subtype Ca2+ channel currents were separated by clamp protocol and selective blockers. T-type Ca2+ channel currents were inhibited with decreasing potency in the order niguldipine > nicardipine > nimodipine > nifedipine (IC50-values 244 nM, 2.5 microM, 9.8 microM, 39 microM), whereas L-type Ca2+ channel currents were blocked with similar potency (IC50 for nicardipine 75 nM). Bay K 8644 increased T-type Ca2+ channel current at nanomolar concentrations (i.e. 95 +/- 16% increase by 300 nM). T-type Ca2+ channel block was completely reversible with exception of the block by niguldipine. Our results indicate a variability of two orders of magnitude in potency of T-type Ca2+ channel block by the dihydropyridine derivatives investigated. It is speculated that the relation between the L- and T-type Ca2+ channel block may determine the therapeutic profile of a dihydropyridine derivative.

Animals↗
PubMed1998

Voltage-activated calcium channels involved in veratridine-evoked [3H]dopamine release in rat striatal slices.

The present study explored the role of different sub-types of voltage-activated Ca2+ channels (VACCs) in mediating veratridine-evoked [3H]dopamine (DA) release from rat striatal slices. The release of [3H]DA evoked by veratridine (25 microM) decreased by 50.6+/-2.9% (n=8) in the absence of calcium and was completely abolished by 1 microM tetrodotoxin. The L-type Ca2+ channel blockers nifedipine (10 microM), nitrendipine (10 microM), diltiazem (10 microM) and verapamil (10 microM) did not modulate this release. Similarly, [3H]DA release was affected neither by the N-type VACC blocker omega-conotoxin-GVIA (1 microM) nor by the selective P-type channel blockers omega-agatoxin-IVA and omega-agatoxin-TK at low nM concentrations (30 nM), indicating no involvement of N- and P-type Ca2+ channels. In contrast, higher concentrations of omega-agatoxin-IVA that would also inhibit Q-type VACCs, blocked the release of [3H]DA by 27.9+/-8.1% (n=5) and 37.5+/-13.6% (n=3) at 0.3 and 1 microM, respectively. In addition, application of the Q-type Ca2+ channel blocker omega-conotoxin-MVIIC (0.01-3 degrees M) reduced [3H]DA release in a concentration-dependent manner, with maximum inhibition of 35.3+/-4.1% at 3 microM (n=5). On the basis of these results, it is concluded that the Ca2+ channels that participate in veratridine-evoked [3H]DA release are Q-type Ca2+ channels.

Animals↗
PubMed1998

Efficacy of glutamate receptor antagonists in the management of functional disorders in cytotoxic brain oedema induced by hexachlorophene.

The hexachlorophene-induced cytotoxic brain oedema is an experimental model of brain damage, suitable for testing cerebroprotective substances (Andreas 1993). In order to examine whether glutamate receptors are involved in mediating functional disorders due to neurotoxic brain damage, we have studied the protective effects of several competitive and non-competitive antagonists using adult male Wistar rats in a simple "ladder-test" for assessing coordinative motor behaviour. Hexachlorophene-induced brain damage was verified by histological examination of the cerebellum with vacuolation of white matter, astrocyte hypertrophy and astrocyte proliferation taken as signs of neurotoxic injury. The non-competitive N-methyl-D-aspartate (NMDA) antagonist dizocilpine maleate (MK-801) decreased the motor disturbance on the first and second day of the "ladder-test" when applied in the doses 0.1 mg/kg and 0.2 mg/kg intraperitoneally for 3 weeks during the hexachlorophene treatment. Acute MK-801 administration (0.1 mg/kg intraperitoneally) after 3 weeks hexachlorophene exposure improved the coordinative motor response only on the first day. When testing the competitive NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5) in the dose 1.0 mg/kg intraperitoneally the motor disturbance was lowered significantly earlier than in spontaneous remission. Similar effects were observed with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the dose of 0.8 mg/kg intraperitoneally, an antagonist interacting both with the strychnine-insensitive binding site for glycine within the NMDA receptor complex and with the kainate(+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor complex. Concurrent MK-801 administration decreased the vacuolation of white matter. The results suggest that NMDA receptors and non-NMDA receptors are involved in development of functional disorders induced by hexachlorophene.

2-Amino-5-phosphonovalerate↗
PubMed1997

Nimodipine and nitrendipine inhibit N-type calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid (NG 108-15) cells.

The effects of nifedipine, niguldipine, nimodipine and nitrendipine on the high K+-induced intracellular Ca2+ ([Ca2+]i) transient in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells were studied by using the fluorescent Ca2+ indicator fura-2. It was observed that nifedipine at the concentration of 50 microM inhibited the high K+-induced [Ca2+]i transient by about 60%; niguldipine at the concentration of 10 microM caused a reduction of about 65% in the high K+-induced calcium signal and a further increase in the concentration up to 50 microM did not result in a significant further reduction in the high K+-induced calcium signal. However, on the other hand, nimodipine and nitrendipine at 50 microM inhibited almost completely the high K+-induced [Ca2+]i transient. Consequently, it was demonstrated in the present study that nimodipine and nitrendipine inhibit both L- and N-type calcium channels and thus seem to be unique among the dihydropyridines examined in their effects on calcium channels in dibutyryl cAMP-differentiated neuroblastoma x glioma hybrid NG 108-15 cells, whereas nifedipine and niguldipine appear to block mainly L-type calcium channels.

Animals↗
PubMed1997

Modulation of potassium-evoked [3H]dopamine release from rat striatal slices by voltage-activated calcium channel ligands: effects of omega-conotoxin-MVIIC.

We examined the involvement of voltage-activated Ca2+ channels (VACCs) on K+(50 mM)-evoked [3H]dopamine ([3H]DA) release from superfused rat striatal slices. Neither nifedipine nor nitrendipine modified K(+)-evoked [3H]DA release, indicating that L-type VACCs are not involved. K(+)-evoked [3H]DA release was partially inhibited by omega-CTx-GVIA and omega-Aga-IVA, and was abolished by 3 microM omega-CTx-MVIIC (IC50 approximately 128 nM), suggesting the involvement of N-, P-, or Q-type VACCs, respectively. Moreover, even subnanomolar concentrations of omega-CTx-MVIIC (0.1-0.5 nM) inhibited K(+)-evoked [3H]DA release by approximately 25%, suggesting the possible involvement of a still not classified (perhaps O-type?) Ca2+ channel subtype. The effects of omega-CTx-MVIIC (10-100 nM) and omega-CTx-GVIA (1 microM) were additive, suggesting that low nanomolar concentrations of omega-CTx-MVIIC does not interact with N-type VACCs. In conclusion, the K(+)-evoked [3H]DA release from rat striatal slices is mediated by entry of Ca2+ through omega-CTx-GVIA sensitive (N-type) as well as through omega-Aga-IVA (P-type) and omega-CTx-MVIIC (probably Q-type) sensitive VACCs.

Animals↗
PubMed1995

Restriction and functional changes of dopamine release in rat striatum from young adult and old rats.

In order to investigate the age-related changes in dopaminergic activity in rats, we have utilized the K(+)- and veratridine-stimulated [14C]dopamine release from striatum in vitro as a functional index of responsiveness to these stimuli in aging. We found that the K(+)-stimulated dopamine release from old (12 months) rats decreased by more than 50% compared to that from young adult rats (3 months). Reserpine (5 mg/kg) led to a pronounced decrease of the K(+)-stimulated dopamine release of young adult as well as old rats. Whereas ouabain (10 mumol/l) decreased the K(+)-stimulated dopamine release from young adult rats, in old rats the K(+)-induced dopamine release was increased up to 250%. However, in old rats which were reserpine pretreated, ouabain was unable to stimulate the K(+)-induced dopamine release. In contrast, the veratridine-stimulated dopamine release of old rats was increased up to 200% compared to that of young adult rats and was highly sensitive to reserpine pretreatment but not to ouabain. However, reserpine did not alter this veratridine-stimulated dopamine release from young adult rats. The present data indicate that the age-related reduction of exocytosis-related, Ca(2+)-dependent release mechanisms (K+) are probably compensated via an increase in Ca(2+)-independent, uptake carrier-mediated release processes (veratridine).

Age Factors↗
PubMed1993

Efficacy of cerebroprotective substances in the management of functional disorders induced by the cytotoxic brain oedema-producing substance hexachlorophene.

The hexachlorophene-induced cytotoxic brain oedema is used as experimental model of brain damage, suitable for testing cerebroprotective substances. It has clinical importance since many brain injuries are accompanied by an oedema. The primary target of the neurotoxin, hexachlorophene, is the neuronal cell membrane, but it also causes secondary effects including a disruption of myelin lamellae, increases in water and sodium content, decreases of potassium content, and vacuolation in the white matter. Rats received orally hexachlorophene 240 mg/kg a day for three weeks by liquid diet. The disruption of coordinative motor response, observed in a specially developed test, was used to characterise hexachlorophene-induced injuries in studies designed to evaluate the potential of cerebroprotective substances. Because of their membranotropic efficacy some nootropic substances with different modes of action were examined. The disturbance of coordinative motor response was restored significantly earlier than in spontaneous remission following administration of piracetam, pyritinol, methyl glucamine orotate, naftidrofuryl, and also under the influence of the calcium antagonists cinnarizine, flunarizine and nifedipine. These results support the therapeutic use of nootropic substances in the management of neurotoxic injuries and brain oedema.

Animals↗
PubMed1987

Ethanol preference and sterotype behavior of rats.

Relations between ethanol consumption and variations of dopaminergic activity expressed by altered apomorphine induced stereotypy behaviour in the rat were investigated. The results of this study show an increase of the stimulating effect of 1 mg/kg apomorphine in nonpreferent ethanol pretreated animals. These changes are present until 72 h after ethanol withdrawal. Ethanol preferent rats do not differ significantly in their stereotypy behaviour from ethanol untreated animals. The observed behavioural alterations will be discussed as an expression of dopaminergic supersensitivity in nigrostriatal structures in nonpreferent rats after chronic ethanol treatment.

Alcohol Drinking↗
PubMed1985

Posthypoxic transmitter release from brain slices and behavioural consequences of hypoxia in rats and mice.

Subsequent to a hypoxic exposure of adult rats and mice the stimulus induced release of dopamine from striatum slices is inhibited for several days. The posthypoxic release inhibition is not restricted to the striatal dopaminergic transmission system especially, but hypoxia causes comparable changes also in other brain regions regarding further transmitter systems. The transmitter release inhibition reflects a significant caudo-rostral gradient of increasing vulnerability of phylogenetically younger brain regions. The consequences of these biochemical changes in the brain following cessation of hypoxia are investigated with regard to behavioural manifestations. Corresponding in time with the inhibition of transmitter release and its restitution the seizure susceptibility is increased when pentetrazol is given in subconvulsive doses. On the other hand, the results of further tests (climbing behaviour, open field, rotarod test, forced-swimming test) do not point to behavioural changes induced particularly by a mild hypoxia.

Animals↗
PubMed1985

Influence of nootropic drugs on drinking behaviour in ethanol-preferring mice and ethanol-induced increase of seizure susceptibility.

The influence of several nootropic drugs (piracetam, pyritinol, meclofenoxat, methylglucamine orotate (MGO) and dihydroergotoxine (DHET) on both the ethanol preference and the enhanced seizure susceptibility after a single dose of ethanol was studied. Piracetam, MGO and DHET reduce the ethanol drinking in ethanol-preferring mice. The enhanced seizure susceptibility after a single dose of ethanol was abolished by piracetam and MGO.

Alcohol Drinking↗
PubMed1984

[Effect of nootropic agents on the lowering of the spasm threshold after a single ethanol application].

We used the effect of ethanol on the convulsion threshold as model of injuriousness to analyse the CNS protective efficacy of nootropics. The CD50 of picrotoxine in mice was significantly diminished in comparision with the controls between 5 and 6 hours after 66 mmol/kg ethanol administered intraperitoneally and between 7 and 8 h after 92.4 mmol/kg. In this moment the administered ethanol was already eliminated; the effect is explained as a reversible consequence of the previous ethanol exposition. The influence of nootropics was examined. Piracetam (0.7 mmol/kg i.p.) as well as methylglucaminorotate (MGO) (0.68 mmol/kg-1 i.p.) suppressed the ethanol effect on the convulsibility, pyritinol (0.82 mmol/kg) was ineffective, and meclophenoxate (1.02 mmol/kg) by itself decreased the convulsions threshold.

Animals↗
PubMed1984

[Dopaminergic sensitivity after ethanol pretreatment and its relation to alcohol preference].

The interactions between ethanol and the central dopaminergic synaptic transmission also refer to the ethanol drinking behaviour. In mice the alteration of the locomotoric activity induced by apomorphine is influenced by ethanol pretreatment for 28 days in a different way referring to drinking behaviour. Ethanol preferent animals do not differ significantly from the ethanol untreated animals in respect to the apomorphine induced locomotion. The nonpreferent animals show, by comparison, a decrease of the sedative effect of low apomorphine doses (0.25 mg/kg; i.p.) and an increase of the stimulating effect of higher doses (1.0 mg/kg; i.p.). These behavioural alterations may be understood as an expression of dopaminergic presynaptic subsensitivity and of a postsynaptic supersensitivity in ethanol pretreated nonpreferent animals.

Alcohol Drinking↗