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  • 1
    Electronic Resource
    Electronic Resource
    Comparison of the effect of cyclic AMP on the content and release of dopamine and 1-methyl-4-phenylpyridinium (MPP+) in PC12 cells (2002)
    Oxford, UK : Blackwell Science Ltd
    Autonomic & autacoid pharmacology 22 (2002), S. 0 
    Details
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 The aim of this work was to investigate the effect of acute and chronic exposure of rat pheochromocytoma (PC12) cells to elevated cAMP, using forskolin, dibutyryl-cAMP (db-cAMP) or isobutylmethylxanthine (IBMX), on endogenous dopamine content and release and on [3H]-1-methyl-4-phenylpyridinium ([3H]-MPP+) uptake and release, under basal conditions and under KCl-stimulation. 2 Cultured PC12 cells synthetized and accumulated large amounts of dopamine, but not noradrenaline or adrenaline. The release of dopamine by the cells was markedly increased in response to 50 mm KCl. 3 Acute and chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), slightly increased the spontaneous release of dopamine and significantly decreased the release induced by 50 mm KCl. 4 Chronic treatment of the cells with forskolin (30 μm), but not IBMX (100 μm), markedly decreased the cellular content of dopamine. 5 Cultured PC12 cells removed and accumulated [3H]-MPP+, which, similarly to dopamine, was released by KCl. 6 Acute treatment of the cells with forskolin (30 μm) or db-cAMP (2.5 mm), but not IBMX (100 μm), slightly increased the spontaneous release, but did not affect KCl-induced release of [3H]-MPP+. On the other hand, chronic treatment of the cells with forskolin produced, on [3H]-MPP+, similar effects to those obtained for dopamine. 7 Acute and chronic treatment of the cells with reserpine (50 nm) produced similar results to those obtained with forskolin on either dopamine or [3H]-MPP+ handling. 8 In conclusion, cAMP, similarly to reserpine, increases the spontaneous release and decreases the KCl-induced release of [3H]-MPP+ and dopamine. This suggests that cAMP impairs the vesicular monoamine transporter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1474-8673.2002.00273.x
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  • 2
    Electronic Resource
    Electronic Resource
    Reconstruction d'un modele prosodique chinois
    Amsterdam : Elsevier
    Poetics 4 (1975), S. 29-45 
    Details
    ISSN: 0304-422X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Linguistics and Literary Studies , Art History
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0304-422X(75)90004-2
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  • 3
    Electronic Resource
    Electronic Resource
    Transport of small organic cations in the rat liver (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 320-326 
    Details
    ISSN: 1432-1912
    Keywords: Rat liver ; Transport of organic cations ; OCT1 ; Type I hepatic transport of cationic drugs ; 1-Methyl-4-phenylpyridinium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The kidneys and the liver are the principal organs for the inactivation of circulating organic cations. Recently, an organic cation transporter (OCT1) has been cloned from rat kidney. In order to answer the question whether OCT1 is involved also in hepatic uptake of organic cations, the pharmacological characteristics of organic cation transport in hepatocytes were compared to the characteristics of transiently expressed OCT1. Primary cultures of rat hepatocytes avidly accumulated the small organic cation 3H-1-methyl-4-phenylpyridinium (3H-MPP+). At equilibrium, the hepatocytes accumulated 3H-MPP+ 56-fold. Initial rates of specific 3H-MPP+ transport in hepatocytes were saturable. The half-saturating concentration was 13 μmol/l. 3H-MPP+ transport was sensitive to quinine (Ki = 0.79 μmol/l) and cyanine863 (Ki = 0.097 µmol/l). Quinine and cyanine863 are known inhibitors of type I hepatic transport of cationic drugs and of renal excretion of organic cations, respectively. To compare the functional characteristics of 3H-MPP+ transport in hepatocytes with those of OCT1, OCT1 has been heterologously expressed and characterized in a mammalian cell line (293 cells). Initial rates of 3H-MPP+ transport were saturable, the Km being 13 μmol/l. The rank order of inhibitory potencies of various inhibitors was almost identical in hepatocytes and 293 cells transiently transfected with OCT1. There was a positive correlation between the Ki's for the inhibition of 3H-MPP+ transport in isolated hepatocytes and transfected 293 cells (r = 0.85; P〈0.01; n = 8). The results indicate that OCT1 is functionally expressed not only in the kidney but also in hepatocytes where it is responsible for the transport of small organic cations which, in the past, have been classified as type I substrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171063
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  • 4
    Electronic Resource
    Electronic Resource
    Uptake of 3H-catecholamines by rat liver cells occurs mainly through a system which is distinct from uptake1 or uptake2 (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 130-142 
    Details
    ISSN: 1432-1912
    Keywords: Key words: Hepatocyte – Catecholamines – Uptake1– Uptake2– Renal organic cation transport – Bilirubin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Isolated rat hepatocytes were incubated with 200 nmol/l 3H-(–)-noradrenaline or 50 nmol/l 3H-(–)-adrenaline for 15 min, in Krebs-Henseleit solution at 37°C, gassed with 95% O2 5% CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited with pargyline (500 μmol/l) and Ro 01-2812 (3,5-dinitropyrocatechol; 2 μmol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact 3H-amine, was measured.   The content of 3H-noradrenaline increased with time of incubation, a plateau having been reached after 15 min of incubation. After 15 min of incubation, the cell:medium ratio for 3H-noradrenaline and 3H-adrenaline was 0.6–0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines – uptake1; 1 μmol/l) did not affect the uptake of either 3H-noradrenaline or 3H-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines - uptake2; 40 μmol/l) slightly inhibited (by 28%) the uptake of 3H-adrenaline, and did not significantly reduce 3H-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 μmol/l) did not influence the amount of either 3H-noradrenaline or 3H-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 μmol/l) decreased by 62% the uptake of 3H-adrenaline into cells but did not significantly affect 3H-noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 μmol/l) produced a significant increase (50%) in the amount of 3H-noradrenaline and 3H-adrenaline present in the cells. When isolated hepatocytes were incubated in a sodium-free medium (sodium being replaced by choline or lithium) there was a very marked inhibition of 3H-noradrenaline and 3H-adrenaline uptake (by 85–97%). An increase in potassium content of the medium (from 6.6 to 50 mmol/l) did not affect the uptake of either 3H-amine into isolated cells.   In conclusion, the uptake of catecholamines by isolated liver cells possesses characteristics that distinguish it from the classic uptake systems for catecholamines (uptake1 and uptake2): (1) it is sodium-dependent but not affected by desipramine; (2) it is only slightly sensitive to corticosterone and not affected by potassium-induced depolarization; (3) it is partially sensitive to cyanine 863. Moreover, the increase of 3H-amine content in the cells in the presence of bilirubin suggests the possibility of catecholamines being excreted from the hepatocytes through the bilirubin transporter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00241086
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  • 5
    Electronic Resource
    Electronic Resource
    Comparison between uptake2 and rOCT1: effects of catecholamines, metanephrines and corticosterone (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 303-309 
    Details
    ISSN: 1432-1912
    Keywords: Key words Catecholamines ; Corticosterone ; Metanephrines ; MPP+ ; rOCT1 ; Uptake2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Active and specialized transmembrane transport systems are responsible for the functional inactivation of catecholamines. Uptake2, the classical extraneuronal uptake system, and rOCT1, a recently cloned organic cation transporter, share a number of properties. The present study was undertaken to investigate putative differences between these two transporters that might clarify their relative physiological roles. Uptake of [3H]MPP+ ([3H]1-methyl-4-phenylpyridi-nium) by Caki-1 cells (to study uptake2) and by primary cultured rat hepatocytes (to study rOCT1) was kinetically and pharmacologically characterized. In both cell types, [3H]MPP+ was avidly taken up and accumulated. All compounds tested (catecholamines, metanephrines and corticosterone) inhibited [3H]MPP+ uptake, albeit with different potencies. In Caki-1 cells, the ranking order of inhibitory potency was: (–)isoprenaline 〉 (–)adrenaline 〉〉 (–)noradrenaline 〉 dopamine. Metanephrine and normetanephrine were equipotent. Corticosterone had an IC50 of 102 nM. In cultured hepatocytes, the ranking order of inhibitory potency was: (–)isoprenaline 〉 dopamine 〉 (–)adrenaline 〉〉 (–)noradrenaline. Metanephrine was about seven times more potent than normetanephrine. Corticosterone had an IC50 of 72 μM, being about 700-fold less potent in inhibiting rOCT1 than uptake2. The results showed that uptake2 and rOCT1 can be clearly distinguished on a functional basis. On the one hand, uptake2 prefers adrenaline among the endogenous catecholamines, whereas rOCT1 has similar affinity for adrenaline and dopamine. On the other hand, corticosterone and normetanephrine are significantly more potent in inhibiting uptake2 than rOCT1. The results are compatible with a possible physiological role of corticosteroids in the modulation of adrenaline effects in tissues equipped with uptake2, without significant interference with the hepatic and renal excretion of catecholamines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005356
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  • 6
    Electronic Resource
    Electronic Resource
    Uptake and metabolism of 3H-adrenaline and 3H-noradrenaline by isolated hepatocytes and liver slices of the rat (1993)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 348 (1993), S. 450-457 
    Details
    ISSN: 1432-1912
    Keywords: Adrenaline ; Noradrenaline ; Uptake1 ; Uptake2 ; Hepatocyte ; Liver slice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated rat hepatocytes were incubated with 0.05 μmol/l or 0.2 μmol/l 3H-(−)-noradrenaline or 0.05 μmol/l 3H-(−)-adrenaline for 15 min and the content of amines as well as the formation of metabolites was measured. The removal Of both amines from the incubation medium was quantitatively similar, and mainly due to metabolism (which represented 96% of the removal of 3H-adrenaline and 98% of the removal of 3H-noradrenaline). O-methylation predominated for 3H-adrenaline: O-methylated and deaminated metabolites (3H-OMDA) and 3H-metanephrine (3H-MN) were the most abundant metabolites, accounting for 63% and 34% of total metabolite formation, respectively. Deamination predominated for 3H-noradrenaline: 3H-OMDA and 3H-dihydroxymandelic acid (3H-DOMA) were the most abundant metabolites, representing respectively 56% and 36% of total metabolite formation. The following activities of monoamine oxidase and catechol-O-methyl transferase were determined for 3H-noradrenaline: kCOMT 0.70±0.15 min−1 and kMAO 2.27±0.14 min−1 In experiments with 3H-noradrenaline, inhibition of monoamine oxidase reduced the formation of 3H-OMDA and deaminated metabolites [3H-dihydroxyphenylglycol (3H-DOPEG) and 3H-DOMA] and increased the formation of 3H-normetanephrine (3H-NMN). Inhibition of catechol-O-methyl transferase, On the Other hand, decreased 3H-NMN and increased 3H-DOPEG formation. When both enzymes were inhibited, the formation of all metabolites was strongly reduced but surprisingly there was no accumulation of 3H-amines in the cells, as the cell: medium ratio for 3H-noradrenaline or 3H-adrenaline was about unity. In experiments with either 3H-noradrenaline or 3H-adrenaline, specific inhibitors of either uptake, or uptake2 produced discrete effects, slightly decreasing the formation of 3H-OMDA and 3H-NMN or 3H-MN, and having no effect on 3H-amine content of the cells. Additional experiments were carried Out with rat liver slices incubated for 15 min with 3H-noradrenaline 0.2 μmol/l. The pattern of metabolism of 3H-noradrenaline (3H-OMDA and 3H-DOMA were the most abundant metabolites) as well as the degree of metabolism of the amine removed from the incubation medium (91% of the removal) were similar to those of the isolated cells. Likewise, there was no accumulation of intact 3H-noradrenaline in the tissue. Moreover, the results obtained with enzyme inhibitors as wells as with uptake inhibitors were similar to those obtained with hepatocytes. In conclusion, isolated hepatocytes remove and metabolize catecholamines very efficiently, being one of the most active systems studied in this respect. Uptake1 and uptake2 are responsible for part of the removal of catecholamines by hepatocytes; the system(s) involved in the remaining removal seem(s) to be active, but possess(es) characteristics that do not allow us to characterize it (them) either as uptake1 or uptake2.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173202
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  • 7
    Electronic Resource
    Electronic Resource
    Uptake of 3H-catecholamines by rat liver cells occurs mainly through a system which is distinct from uptake1 or uptake2 (1994)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 350 (1994), S. 130-142 
    Details
    ISSN: 1432-1912
    Keywords: Hepatocyte ; Catecholamines ; Uptake1 ; Uptake2 ; Renal organic cation transport ; Bilirubin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Isolated rat hepatocytes were incubated with 200 nmol/l 3H-(−)-noradrenaline or 50 nmol/l 3H(−)-adrenaline for 15 min, in Krebs-Henseleit solution at 37°C, gassed with 95% O2 5010 CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited withpargyline (500 μmol/l)and Ro 01-2812 (3,5-dinitropyrocatechol; 2 μol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact 3H-amine, was measured. The content of 3H-noradrenaline increased with time of incubation, a plateau having been reached after 15 min of incubation. After 15 min of incubation,the cell: medium ratio for 3H-noradrenaline and 3H-adrenaline was 0.6–0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines — uptake,; 1 μmol/l) did not affect the uptake of either 3H-noradrenaline or 3H-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines — uptake2; 40 μmol/l) slightly inhibited (by 28%) the uptake of 3H-adrenaline, and did not significantly reduce 3H-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 μmol/l) did not influence the amount of either 3H-noradrenaline or 3H-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 μmol/l) decreased by 62% the uptake of 3H-adrenaline into cells but did not significantly affect 3H-noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 μol/l) produced a significant increase (50%) in the amount of 3H-noradrenaline and 3H-adrenaline present in the cells. When isolated hepatocytes were incubated in a sodium-free medium (sodium being replaced by choline or lithium) there was a very marked inhibition of 3H-noradrenaline and 3H-adrenaline uptake (by 85–97%). An increase in potassium content of the medium (from 6.6 to 50 mmol/l) did not affect the uptake of either 3H-amine into isolated cells. In conclusion, the uptake of catecholamines by isolated liver cells possesses characteristics that distinguish it from the classic uptake systems for catecholamines (uptake1 and uptake2): (1) it is sodium-dependent but not affected by desipramine; (2) it is only slightly sensitive to corticosterone and not affected by potassium-induced depolarization; (3) it is partially sensitive to cyanine 863. Moreover, the increase of 3H-amine content in the cells in the presence of bilirubin suggests the possibility of catecholamines being excreted from the hepatocytes through the bilirubin transporter. PhD student with a grant from JNICT (Programa Ciência)
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00241086
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  • 8
    Electronic Resource
    Electronic Resource
    Discovery of the short γ -ray burst GRB 050709 (2005)
    [s.l.] : Nature Publishing Group
    Nature 437 (2005), S. 855-858 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Gamma-ray bursts (GRBs) fall into two classes: short-hard and long-soft bursts. The latter are now known to have X-ray and optical afterglows, to occur at cosmological distances in star-forming galaxies, and to be associated with the explosion of massive stars. In contrast, the distance scale, ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/nature04213
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  • 9
    Electronic Resource
    Electronic Resource
    Nigral grafts in neonatal rats protect from aphagia induced by subsequent adult 6-OHDA lesions: the importance of striatal location (1990)
    Springer
    Experimental brain research 80 (1990), S. 172-176 
    Details
    ISSN: 1432-1106
    Keywords: Neonatal grafts ; Nigral transplant ; Dopamine ; Aphagia ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have shown that dopamine-rich nigral grafts, implanted bilaterally into the intact neonatal brain, will provide some protection from the eating disorders induced by subsequent nigrostriatal 6-OHDA lesions. This has been repeated in the present study using unilaterally transplanted nigral grafts. Following adult lesions, the control animals displayed the full syndrome of aphagia, adipsia and akinesia. By contrast, 37% of the rats in the transplanted group recommenced eating following the adult lesion. Recovery was related to the size and position of the graft: protection was associated in particular with transplants located in the posterior-ventral neostriatum. The results are discussed in terms of specific patterns of graft-host interaction that may underlie protection of the regulation of eating from the loss of forebrain dopamine systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228858
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  • 10
    Electronic Resource
    Electronic Resource
    Transport of small organic cations in the rat liver The role of the organic cation transporter OCT1 (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 320-326 
    Details
    ISSN: 1432-1912
    Keywords: Key words Rat liver ; Transport of organic cations ; OCT1 ; Type I hepatic transport of cationic drugs ; 1-Methyl-4-phenylpyridinium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The kidneys and the liver are the principal organs for the inactivation of circulating organic cations. Recently, an organic cation transporter (OCT1) has been cloned from rat kidney. In order to answer the question whether OCT1 is involved also in hepatic uptake of organic cations, the pharmacological characteristics of organic cation transport in hepatocytes were compared to the characteristics of transiently expressed OCT1. Primary cultures of rat hepatocytes avidly accumulated the small organic cation 3H-1-methyl-4-phenylpyridinium (3H-MPP+). At equilibrium, the hepatocytes accumulated 3H-MPP+ 56-fold. Initial rates of specific 3H-MPP+ transport in hepatocytes were saturable. The half-saturating concentration was 13 μmol/l. 3H-MPP+ transport was sensitive to quinine (Ki = 0.79 μmol/l) and cyanine863 (Ki = 0.097 μmol/l). Quinine and cyanine863 are known inhibitors of type I hepatic transport of cationic drugs and of renal excretion of organic cations, respectively. To compare the functional characteristics of 3H-MPP+ transport in hepatocytes with those of OCT1, OCT1 has been heterologously expressed and characterized in a mammalian cell line (293 cells). Initial rates of 3H-MPP+ transport were saturable, the Km being 13 μmol/l. The rank order of inhibitory potencies of various inhibitors was almost identical in hepatocytes and 293 cells transiently transfected with OCT1. There was a positive correlation between the Ki’s for the inhibition of 3H-MPP+ transport in isolated hepatocytes and transfected 293 cells (r = 0.85; P〈0.01; n = 8). The results indicate that OCT1 is functionally expressed not only in the kidney but also in hepatocytes where it is responsible for the transport of small organic cations which, in the past, have been classified as type I substrates.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171063
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