Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • Neuronal uptake  (7)
  • Isoprenaline  (5)
  • Ligand-gated ion channels  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Extraneuronal removal, accumulation and O-methylation of isoprenaline in the perfused heart (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 283 (1974), S. 191-218 
    Details
    ISSN: 1432-1912
    Keywords: Isoprenaline ; Extraneuronal Uptake ; Extraneuronal O-Methylation ; Rat Heart ; Removal of Isoprenaline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Isolated rat and guinea-pig hearts were perfused with 0.95 μM (±)-isoprenaline or 3H(±)-isoprenaline, a catecholamine which is taken up by extraneuronal mechanisms only. From measurements of the arterio-nevous difference (by fluorimetry and by scintillation counting, respectively) the rate of removal of the amine from the perfusion fluid was measured; in addition, the rate of appearance of its metabolite (3-O-methyl-3H-isoprenaline; 3H-OMI) was determined in the venous effluent as well as the accumulation of 3H-isoprenaline and 3H-OMI in the heart. 2. Experiments with sodium thiocyanate and 14C-sorbitol showed that these agents distributed into the extracellular space (about 350 μl/g; t/2 for efflux of about 1.2 min) and into ventricular and atrial cavities (about 1500 μl/g; t/2 for efflux of 0.1 to 0.2 min). 3. The removal of 3H-isoprenaline from the perfusion fluid declined biphasically with time; after an initial rapid decline the rate of removal approached steadystate levels within about 30 min. After block of COMT (by the presence of 100 μM U-0521) the second phase of decline approached zero. In the absence of U-0521 the steady-state rate of removal was 10 times higher in rat than in guinea-pig hearts; in the presence of U-0521 the approach to zero was faster for guinea-pig than for rat hearts. 4. When COMT was intact, 3H-OMI appeared in the venous effluent, first at a rapidly increasing rate, from the 9th minute of perfusion onward at a steady rate which was identical with the steady-state rate of removal of 3H-isoprenaline. No 3H-OMI was detected after block of COMT. 5. The accumulation of 3H-isoprenaline in the heart reached a steady level within about 30 min; block of COMT increased the time required for approach to steady levels and increased the accumulation of 3H-isoprenaline in the rat (but not in the guinea-pig) heart. When COMT was intact, the accumulation of 3H-OMI in the heart reached steady-state levels within 10 min. 6. The time-dependent decline of the rate of removal of 3H-isoprenaline by hearts whose COMT had been inhibited was due to a time-dependent increase of the rate of efflux of the amine from the stores; there did not seem to be any change in the rate of gross influx. 7. Isoprenaline-induced ventricular fibrillation reduced the rate of O-methylation of 3H-isoprenaline significantly. 8. Perfusion of hearts with 0.095 μM (±)-isoprenaline resulted in a significantly greater accumulation of the amine in rat than in guinea-pig and rabbit hearts.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00501145
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Solubilization and characterization of the3H-desipramine binding site of rat phaeochromocytoma cells (PC12-cells) (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 412-417 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal uptake ; Desipramine binding sites ; Membrane solubilization ; Clonal rat phaeochromocytoma cells (PC12)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 3H-Desipramine binding sites of the plasma membranes of rat phaeochromocytoma cells (PC12-cells) were solubilized with the nonionic detergent digitonin (0.5%). With the method described here, the binding characteristics of the desipramine binding site were essentially unaltered by solubilization. Binding of3H-desipramine to the solubilized binding site showed the following characteristics: (1)3H-desipramine bound with high affinity (K D=16.6 nmol/l) to a single class of noninteracting (Hill-coefficient=1.01) binding sites; (2) binding was reversible; (3) binding of unlabelled desipramine had the same dissociation constant as had3H-desipramine; (4) increasing concentrations of sodium- and chloride-ions stimulated the binding of3H-desipramine; (5) binding was inhibited by various inhibitors and substrates of neuronal uptake of noradrenaline; and (6) inhibition of binding by the optical isomers of cocaine, oxaprotiline, and amphetamine showed marked stereoselectivity (with preference for (−)cocaine, (+)oxaprotiline, and (+)amphetamine). The finding that the binding of3H-desipramine to the solubilized binding site was dependent on sodium and chloride, as the neuronal uptake of noradrenaline is, and the finding that all substrates of uptake1 inhibited the binding of3H-desipramine, is consistant with the view that desipramine binds to the substrate recognition site of the neuronal carrier for noradrenaline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569379
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    The rate constants for the efflux of deaminated metabolites of 3H-dopamine from the perfused rat heart (1980)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 314 (1980), S. 231-235 
    Details
    ISSN: 1432-1912
    Keywords: Rat heart ; 3H-Dopamine ; Neuronal uptake ; Extraneuronal uptake ; Rate constants for efflux ; Dopamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Hearts of rats pretreated with reserpine and FLA 63 were perfused for 30 min with 1 μmol/l 3H-dopamine and in the presence of an inhibitor of either neuronal (30 μmol/l cocaine) or extraneuronal uptake (87 μmol/l corticosterone). From the rate at which the deaminated metabolites appeared in the venous perfusate and from the tissue content of the metabolites at the end of the perfusion rate constants for efflux (k-values) were determined. The k-values for the deaminated metabolites of dopamine did not differe when the deamination of dopamine was restricted to either extraneuronal or neuronal sites. However, marked differences existed between the rate constant for efflux of the deaminated acid DOPAC (dihydroxyphenylacetic acid) and the glycol DOPET (dihydroxyphenylethanol). The relationship between the apparent lipophilicity and the rate constant for efflux of DOPAC fitted very well with that reported for other metabolites of catecholamines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498544
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    The neuronal noradrenaline transport system of PC-12 cells: Kinetic analysis of the interaction between noradrenaline, Na+ and Cl− in transport (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 333 (1986), S. 246-252 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal uptake ; Noradrenaline ; PC-12 cells ; Sodium ; Chloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The uptake of 3H-noradrenaline into reserpine-pretreated PC-12 cells (a clonal cell line which possesses “uptake1”) was abolished when at high extracellular Cl−1 all the extracellular Na+ was replaced by Tris+ and when at high extracellular Na+ all the extracellular Cl− was replaced by isethionate. Increases in the external Cl− concentration (at a fixed high Na+ concentration) progressively increased the uptake of 3H-noradrenaline. The same was found with increase in the external Na+ concentration (at a fixed high Cl− concentration). From the anions tested only Br− and SCN− were able to partially mimic the transport-stimulating effect of Cl− (with about 40% and 20% effectiveness, respectively). When chloride was replaced by nitrate or larger anions such as sulphate, methylsulphate or isethionate, virtually no transport of 3H-noradrenaline was observed. The initial rate of uptake of 3H-noradrenaline showed saturation with increasing concentrations of noradrenaline when determined at several fixed concentrations of either Na+ or Cl−. The apparent K m for noradrenaline transport ( $$K_{m_{NA} } $$ ) progressively decreased and the $$V_{max_{NA} } $$ increased with increases in the concentration of Na+ (at a high concentration of Cl−) or Cl− (at a high concentration of Na+). The stimulation of the initial rate of uptake of 3H-noradrenaline by increasing concentrations of either Na+ or Cl− obeyed saturation kinetics when determined at several concentrations of noradrenaline. The concentration of Na+ (or Cl−) which caused half-maximal stimulation of uptake (i.e., the apparent $$K_{m_{Na + } } $$ and the apparent $$K_{m_{Cl - } } $$ ) decreased with increases in the concentration of noradrenaline. These results strongly suggest that Na+ and Cl− are co-transported with noradrenaline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00512937
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    The O-methylation of extraneuronally stored isoprenaline in the perfused heart (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 283 (1974), S. 245-261 
    Details
    ISSN: 1432-1912
    Keywords: Isoprenaline ; Extraneuronal COMT ; Uptake2 ; Corticosterone ; Extraneuronal Compartments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rat hearts were perfused with 0.95 or 23.8 μM 3H-(±)-isoprenaline for 30 min; efflux curves were determined for total radioactivity, 3H-isoprenaline and 3H-O-methylisoprenaline during wash out with amine-free solution. 2. The efflux curves indicated that most or all of the COMT activity was associated with compartment III of Bönisch et al. (1974). Most of the metabolite appearing in the wash out solution was formed during wash out. 3. The efflux curves for the metabolite (3H-OMI) were convex. The convexity was much more pronounced after perfusion with 23.8 μM than after perfusion with 0.95 μM 3H-isoprenaline. 4. On addition of 20 μM corticosterone to the wash out solution, the rate of efflux of 3H-isoprenaline was reduced but not that of 3H-OMI; in addition, the appearance of the convexity of the efflux curve for 3H-OMI was delayed. 5. In order to explain these phenomena, it is suggested that, during perfusion with 0.95 μm or more of catecholamine, the rate of uptake into compartment III is substantially higher than the rate of O-methylation. Consequently, unchanged amine can accumulate in compartment III and saturate COMT. During wash out the enzyme becomes desaturated, and the convex shape of the efflux curve for the product (3H-OMI) ensues. 6. The O-methylating capacity of the guinea-pig hearts is considerably smaller than that of the rat heart.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499186
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 121-131 
    Details
    ISSN: 1432-1912
    Keywords: Isoprenaline ; Extraneuronal uptake ; Corticosterone ; Inhibition of extraneuronal uptake ; Extraneuronal efflux ; Steady-state kinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To simultaneously determine the kinetics of removal, O-methylation and accumulation of 3H-isoprenaline, isolated rat hearts were perfused for 4 min with various concentrations of 3H-isoprenaline. The apparent K m for the O-methylation of 3H-isoprenaline (3.3±0.5 μM) was more than one order of magnitude lower than the corresponding value for the accumulation of unchanged amine (71.3±7.1 μM). The apparent K m for removal was very similar to that for accumulation (63.2±5.9 μM). At perfusion concentrations higher than 25 μM, i.e. when O-methylation was saturated, removal virtually equalled accumulation. However, at low substrate concentrations removal of 3H-isoprenaline was overwhelmingly followed by O-methylation; this led to a marked difference between rates of removal and those of accumulation. When initial rates of uptake of 3H-isoprenaline were determined after 1.5 min of perfusion of the hearts by the method of Graefe et al. (1978), the uptake of 3H-isoprenaline consisted of two components: a nonsaturable and a saturable (after subtraction of the nonsaturable component from the total uptake). The kinetic constants of the saturable component of uptake were higher than those obtained after 4 min perfusion (see above) (K m : 110±19 μM; V max: 80±4 nmoles·g−1·min−1). Corticosterone competitively inhibited the saturable component of uptake of 3H-isoprenaline (K m : 1.2 μM). During wash out of accumulated 3H-isoprenaline, O-methylation took place predominantly in one of the two extraneuronal compartments. The efflux of 3-O-methyl-3H-isoprenaline (3H-OMI), the O-methylated metabolite of 3H-isoprenaline, was characterized by a half time of about 1.2 min. O-methylation accelerated the loss of radioactivity from the tissue during wash out. The extraneuronal uptake of 3H-isoprenaline was characterized as a “pump and leak” system by means of steady-state kinetics of accumulation of 3H-isoprenaline. Half saturation of the steady-state accumulation was observed at a concentration of 104.5 ±18.5 μM 3H-isoprenaline; the leak component was characterized by a rate constant of 0.0359 min−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508057
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Inhibition of 5-HT3 receptor function by imidazolines in mouse neuroblastoma cells: potential involvement of σ2 binding sites (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 245-252 
    Details
    ISSN: 1432-1912
    Keywords: Key words N1E-115 cells ; Imidazoline receptor ; σ-Binding site ; 5-HT3 receptor ; Ligand-gated ion channels ; [3H]DTG binding sites ; [3H]GR65630 binding sites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of several imidazolines and σ-site ligands on cation influx through the 5-HT3 receptor channel in N1E-115 mouse neuroblastoma cells was studied by measuring the 2-min influx of the organic cation [14C] guanidinium induced by 1 μM 5-HT (in the presence of 10 μM substance P in all experiments). In addition, we determined specific binding of [3H]DTG (1,3-di(2-tolyl)- guanidine), a selective σ-site radioligand, and [3H] GR65630 (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone), a selective 5-HT3 receptor antagonist, to membranes prepared from N1E-115 cells. The 5-HT-induced [14C]guanidinium influx was inhibited by the imidazolines, ondansetron, antazoline, idazoxan, BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline), cirazoline, naphazoline, clonidine and by the guanidine agmatine, but not by the catecholamine adrenaline. The inhibitory effect of the imidazolines on cation influx through the 5-HT3 receptor channel was mimicked by the σ-site ligands, (±)-ifenprodil, (+)-3-PPP ((R)-3-(3-hydroxy-phenyl)-N-propylpiperidine), DTG (1,3-di-tolyl-guanidine), haloperidol, dizocilpine, and ketamine as well as by the polyamines, arcaine and spermidine. – Ondansetron inhibited [3H]GR65630 binding with high affinity, whereas inhibition of binding of this radioligand to the 5-HT3 receptor by antazoline, BDF 6143, idazoxan, cirazoline, (±)-ifenprodil, (+)-3-PPP, DTG and haloperidol occurred in the high micromolar range. In the competition experiments with [3H]DTG, (±)-ifenprodil, haloperidol, unlabelled DTG, BDF 6143 and (+)-3-PPP inhibited binding of the radioligand at moderate affinity (Ki values in the range of 1 μM or lower), whereas ondansetron, antazoline, idazoxan, cirazoline, naphazoline, clonidine, tolazoline, efaroxan, RX821002 (2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazo- line), ketamine and spermidine exhibited affinity in the high micromolar or millimolar range only. Comparison of the potencies of the ligands (pIC50% values) in inhibiting 5-HT-induced [14C]guanidinium influx with their affinities (pKi values) at the 5-HT recognition sites of the 5-HT3 receptor and at the σ2-sites of the N1E-115 cells by means of multiple regression analysis revealed a significant correlation with the affinities at both sites. In conclusion, our data suggest that imidazolines and σ-ligands, which as a rule possess low affinity for the 5-HT recognition site of the 5-HT3 receptor, may be assumed to exert their inhibitory effect on cation influx through the 5-HT3 receptor channels, at least in part, by interacting with σ2-binding sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171054
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Inhibition of 5-HT3 receptor function by imidazolines in mouse neuroblastoma cells: potential involvement of σ2 binding sites (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 245-252 
    Details
    ISSN: 1432-1912
    Keywords: N1E-115 cells ; Imidazoline receptor ; σ-Binding site ; 5-HT3 receptor ; Ligand-gated ion channels ; [3H]DTG binding sites ; [3H]GR65630 binding sites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The influence of several imidazolines and σ-site ligands on cation influx through the 5-HT3 receptor channel in NIE-115 mouse neuroblastoma cells was studied by measuring the 2-min influx of the organic cation [14C] guanidinium induced by 1 μM 5-HT (in the presence of 10 μM substance P in all experiments). In addition, we determined specific binding of [3H]DTG (1,3-di(2-tolyl)-guanidine), a selective σ-site radioligand, and [3H] GR65630 (3-(5-methyl-1H-imidazol-4-yl)-1-(1-methyl-1H-indol-3-yl)-1-propanone), a selective 5-HT3 receptor antagonist, to membranes prepared from NIE-115 cells. The 5-HT-induced [14C]guanidinium influx was inhibited by the imidazolines, ondansetron, antazoline, idazoxan, BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline), cirazoline, naphazoline, clonidine and by the guanidine agmatine, but not by the catecholamine adrenaline. The inhibitory effect of the imidazolines on cation influx through the 5-HT3 receptor channel was mimicked by the σ-site ligands, (±)-ifenprodil, (+)-3-PPP ((R)-3-(3-hydroxyphenyl)-N-propylpiperidine), DTG (1,3-di-tolyl-guanidine), haloperidol, dizocilpine, and ketamine as well as by the polyamines, arcane and spermidine. — Ondansetron inhibited [3H]GR65630 binding with high affinity, whereas inhibition of binding of this radioligand to the 5-HT3 receptor by antazoline, BDF 6143, idazoxan, cirazoline, (±)-ifenprodil, (+)-3-PPP, DTG and haloperidol occurred in the high micromolar range. In the competition experiments with [3H]DTG, (±)-ifenprodil, haloperidol, unlabelled DTG, BDF 6143 and (+)-3-PPP inhibited binding of the radioligand at moderate affinity (Ki values in the range of 1 μM or lower), whereas ondansetron, amazoline, idazoxan, cirazoline, naphazoline, clonidine, tolazoline, efaroxan, RX821002 (2-[2-(2-methoxy-1,4-benzodioxanyl)]imidazoline), ketamine and spermidine exhibited affinity in the high micromolar or millimolar range only. Comparison of the potencies of the ligands (pIC50% values) in inhibiting 5-HT-induced [14C]guanidinium influx with their affinities (pKi values) at the 5-HT recognition sites of the 5-HT3 receptor and at the σ2-sites of the N1E-115 cells by means of multiple regression analysis revealed a significant correlation with the affinities at both sites. In conclusion, our data suggest that imidazolines and σ-ligands, which as a rule possess low affinity for the 5-HT recognition site of the 5-HT3 receptor, may be assumed to exert their inhibitory effect on cation influx through the 5-HT3 receptor channels, at least in part, by interacting with σ2-binding sites.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171054
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Analysis of the compartments involved in the extraneuronal storage and metabolism of isoprenaline in the perfused heart (1974)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 283 (1974), S. 223-244 
    Details
    ISSN: 1432-1912
    Keywords: Isoprenaline ; Extraneuronal COMT ; Uptake2 ; Corticosterone ; Extraneuronal Compartments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rat hearts were perfused with various concentrations of 3H-(±)-isoprenaline, and initial rates were determined for the removal of the amine from the perfusion fluid and for its O-methylation. Both removal and O-methylation obeyed Michaelis-Menten kinetics, K m and V max being 21 μM and 38 nmoles · g−1 · min−1 for the former, and 2.9 μM and 1.7 nmoles · g−1 · min−1 for the latter. After block of COMT the kinetic constants for removal (which equals accumulation under these conditions) were about the same as before. The kinetics of O-methylation seem to differ strikingly from those of accumulation of unchanged amine. 2. Corticosterone and 3-O-methylisoprenaline were about equipotent in antagonizing the accumulation and O-methylation of isoprenaline in the rat heart during perfusion with 3H-isoprenaline. 3. U-0521 (dihydroxy-2-methyl propiophenone; 100 μM) was used as a blocker of COMT. In addition it was found to be a weak inhibitor of the extraneuronal uptake of isoprenaline (K i =230 μM). 4. After block of COMT and subsequent to perfusion of the heart with 0.95 μM 3H-isoprenaline, efflux curves were determined during wash out with amine-free solution. Four compartments were detected (in order of increasing half time of efflux): I represented the fluid in dead space, cardiac cavities and large vessels; II equalled the extracellular space; III and IV represented extraneuronal storage sites. Corticosterone impaired the filling of compartments III and IV when present during filling. Both corticosterone and 3-O-methylisoprenaline (OMI) delayed the efflux from compartment III when present in the wash out solution only. 5. Experiments with guinea-pig hearts showed qualitative similarities between these and rat hearts. However, the storage and the O-methylating capacity of the guinea-pig heart was considerably smaller than that of the rat heart. 6. Rat ventricle slices (exposed to 0.95 μM 3H-(±)-isoprenaline for 30 min) were compared with perfused hearts. While the accumulation of 3H-isoprenaline was about 1/4, the total formation of 3H-OMI was only 1/50 of that determined for the perfused heart. This low rate of formation of 3H-OMI was also observed for slices of aorta, vas deferens and spleen, while slices of salivary glands had a high O-methylating capacity. Apparently, perfusion of the heart provides optimal access to the O-methylating compartment which may be located in vascular smooth muscle.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00499185
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    The influence of the rate of perfusion on the kinetics of neuronal uptake in the rabbit isolated heart (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 275-283 
    Details
    ISSN: 1432-1912
    Keywords: Rate of perfusion ; Neuronal uptake ; Accessibility of neuronal uptake sites ; Perfusion pressure ; Rabbit heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rabbit hearts (with monoamine oxidase and catechol-O-methyl transferase inhibited) were obtained from reserpine-pretreated animals. They were perfused at rates ranging from 1.3–11.3 ml·g−1·min−1 with 0.1 mM 14C-sorbitol and various concentrations of 3H-(−)noradrenaline (NA). From measurements of the arterio-venous concentration difference of 3H and 14C activity the removal of NA and sorbitol from the perfusion fluid was followed for 2–3 min at intervals of 5 s. The uptake of NA into intracellular spaces of the heart (known to be over-whelmingly into sympathetic nerve terminals) was obtained by subtracting the removal of sorbitol from that of NA. If was cumulated and plotted against time. 2. The progress curves of NA uptake were sigmoid in shape: following a lag period, uptake proceeded at first at a constant initial rate and from then on at gradually decreasing rates. Irrespective of the NA concentration used, the lag period became shorter and the initial rate of uptake increased whenever the rate of perfusion was increased. Furthermore, at high rates of perfusion the initial rate was maintained for a shorter time than at low ones. 3. At any given perfusion rate, the initial rates of NA uptake obeyed Michaelis-Menten kinetics. While changes of the rate of flow did not alter the apparent K m (range: 2.2–2.4 μM), a rectangular hyperbolic relationship was found between V max and the perfusion rate. The V max was half-maximal at a rate of flow of 2.7 ml·g−1·min−1 and approached a maximum value of 9.0 nmoles·g−1·min−1. 4. From the lack of change in the K m it can be concluded that the uptake sites of the perfused heart are functionally arranged in parallel. The change in V max, on the other hand, indicate that the accessibility of the sites is limited by the rate of perfusion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508296
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...