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  • 1985-1989  (3)
  • 1980-1984  (1)
  • Anaesthetized rabbit  (2)
  • Veratridine  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Sodium-dependence of the saturability of carrier-mediated noradrenaline efflux from noradrenergic neurones in the rat vas deferens (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 332 (1986), S. 131-134 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal efflux ; Noradrenaline carrier ; Veratridine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The carrier-mediated transport of 3H-noradrenaline out of noradrenergic neurones was studied in vasa deferentia obtained from rats after pretreatment with reserpine and pargyline (to inhibit vesicular storage and monoamine oxidase, respectively). The tissue was first preincubated with various concentrations of 3H-noradrenaline (0.3–100 μmol/l; 30 min) and then washed out for 110 min with amine-free medium. During the last 10 min of washout, carrier-mediated neuronal efflux of 3H-noradrenaline was elicited by exposure to either Na+-free medium or 100 μmol/l veratridine; it was measured at 1-min intervals. 2. While the peak rates of carrier-mediated 3H-noradrenaline efflux elicited by Na+-free medium were linearly related to the 3H-noradrenaline content of the tissue (which cannot be raised beyond a certain maximal value, since uptake is saturable), those evoked in response to veratridine approached saturation as the 3H-noradrenaline level in the tissue was raised. Hence, saturation of 3H-noradrenaline outward transport was demonstrated at high (exposure to veratridine), but not at low (exposure to Na+-free medium) intraneuronal Na+ concentrations. 3. The results indicate that the K m for the mediated outward transport of noradrenaline across the plasma membrane of noradrenergic neurones is inversely related to the internal Na+ concentration, just as the K m for the mediated inward transport of noradrenaline (i.e., the neuronal noradrenaline uptake) is inversely related to the external Na+ concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00511402
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  • 2
    Electronic Resource
    Electronic Resource
    Tetrodotoxin-sensitive and-resistant effects of veratridine on the noradrenergic neurone of the rat vas deferens (1983)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 324 (1983), S. 264-270 
    Details
    ISSN: 1432-1912
    Keywords: Veratridine ; Exocytotic release ; Neuronal efflux ; “Reserpine-like” effects ; Rat vas deferens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1) The veratridine-induced release of 3H-noradrenaline from noradrenergic neurones was examined in the isolated vas deferens of either untreated or reserpine plus pargyline-pretreated rats. The rat vas deferens, whose catechol O-methyltransferase was inhibited, was first incubated with 0.4 μmol/l 3H-(−)noradrenaline (30 min) and then washed repeatedly with amine-free solution. After 120 min (i.e., well after the efflux of tritium from the tissue had reached a steady level and was predominantly of neuronal origin), washout was continued in the presence of veratridine for further 10–15 min. 2) In vasa deferentia of untreated rats, variatridine (1–100 μmol/l) caused a concentration-dependent increase in the efflux of tritium. At high concentrations of the drug (30 or 100 μmol/l), this increase in efflux was peak-like during the first 3 min (“peak response”) and then fell to a plateau (“plateau response”). In the presence of veratridine, unchanged 3H-noradrenaline accounted for about 75% of the tritium efflux (the rest being represented by deaminated 3H-catechol metabolites). 3) The “peak response” to veratridine (100 μmol/l) was abolished by tetrodotoxin (TTX; 1 μmol/l) or the absence of external Ca2+. Cocaine (10 μmol/l) affected neither the “peak response” as such nor the contribution by 3H-noradrenaline to the efflux of tritium during that response. Hence, the “peak response” was due to exocytotic release of 3H-noradrenaline from the neurone. 4) The “plateau response” to veratridine (100 μmol/l) was unaffected by the absence of external Ca2+, largely resistant to TTX (1 μmol/l) and moderately reduced by cocaine. However, both TTX and cocaine drastically changed the composition of the radioactivity during the “plateau response”: they greatly reduced or even abolished the efflux of unchanged 3H-noradrenaline and markedly increased the efflux of deaminated 3H-metabolites. Hence, the “plateau response” represented a “reserpine-like” vesicular effect of varatridine; the ensuing 3H-noradrenaline efflux out of the neurone was mediated by the neuronal amine carrier. 5) After pretreatment with reserpine (to inhibit vesicular uptake) and pargyline (to inhibit monoamine oxidase), veratridine (100 μmol/l) elicited a phasic, peak-like increase in the efflux of tritium (about 90% of which was unchanged 3H-noradrenaline). This response to veratridine was abolished by TTX (1 μmol/l) and unaffected by the absence of external Ca2+; moreover, it was greatly reduced by either cocaine (10 μmol/l) or desipramine (1 μmol/l) and, hence brought about by carrier-mediated outward transport across the axonal membrane. 6) It is concluded that, in addition to its well-known action on the fast sodium channel, veratridine somehow increases the leakage of noradrenaline from storage vesicles; this “reserpine-like” effect of veratridine is resistant to TTX and therefore not a consequence of the drug-induced changes in the sodium permeability of the axolemma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00502621
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  • 3
    Electronic Resource
    Electronic Resource
    Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit (1988)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 338 (1988), S. 361-367 
    Details
    ISSN: 1432-1912
    Keywords: Noradrenaline clearance ; Fractional noradrenaline extraction ; Differently 3H-labelled noradrenaline ; Plasma DOPEG ; Anaesthetized rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Rabbits were anaesthetized with urethane/chloralose and infused intravenously with trace amounts of 3H-2,5,6-, 3H-7,8- or 3H-7-(-)noradrenaline either without or with unlabelled (\t-)noradrenaline being simultaneously infused (0.2 gg kg\t-1 min\t-1). To obtain clearance values and extraction ratios for the pulmonary, systemic and total circulation, steady-state concentrations of infused noradrenaline were determined in mixed central venous (C v) and arterial (C v) plasma. Heart rate and blood pressure were recorded via the carotid artery, and the dye dilution method was used to determine the cardiac output of plasma. 2. The simultaneous infusion of unlabelled noradrenaline, which increased plasma levels of noradrenaline by a factor of 5, had no significant effect on either heart rate, blood pressure or cardiac output (when determined at steady state of the noradrenaline infusion). 3. The simultaneous infusion of unlabelled noradrenaline did not affect the clearance values of any of the three type of 3H-noradrenaline. Moreover, the clearances of the various types of 3H-noradrenaline were virtually identical and agreed with that of unlabelled noradrenaline. However, the clearance of labelled and unlabelled noradrenaline from arterial plasma was 1.15 times higher than that from central venous plasma. This factor corresponded to the ratio of C v/C a and pointed towards net removal of noradrenaline from the pulmonary circulation. 4. The fractional pulmonary extractions [1 - (C a/C a)] of the three types of 3H-noradrenaline did not differ from each other and were not affected by the simultaneous infusion of unlabelled noradrenaline. Moreover, the fractional pulmonary extraction of endogenous noradrenaline resembled that of infused 3H- and unlabelled noradrenaline, suggesting that there was little, if any, overflow of endogenous noradrenaline into plasma during passage through the pulmonary circulation. 5. From the clearance of noradrenaline from mixed central venous plasma, its fractional pulmonary extraction and the cardiac output of plasma estimates of the following steady-state kinetic parameters for infused noradrenaline were obtained: pulmonary, systemic as well as total body clearance (13.4, 67.9, 72.6 ml kg\t-1 min\t-1) and fractional extraction (0.128, 0.650, 0.695). The rates at which infused noradrenaline was eliminated from the pulmonary and systemic circulation amounted to 18.4 and 81.6% of the total body elimination rate, respectively. 6. The infusion of unlabelled noradrenaline increased plasma levels of 3,4-dihydroxyphenylglycol (DOPEG) by a factor of 1.2. DOPEG concentrations in arterial plasma were 4.9% higher than those in mixed central venous plasma. Hence, there was some net formation of DOPEG in the pulmonary circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00172110
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  • 4
    Electronic Resource
    Electronic Resource
    Plasma 3,4-dihydroxyphenylglycol as a tool to assess the role of neuronal uptake in the anaesthetized rabbit (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 340 (1989), S. 726-732 
    Details
    ISSN: 1432-1912
    Keywords: 3,4-Dihydroxyphenylglycol ; Presynaptic noradrenaline metabolism ; Noradrenaline infusion ; Desipramine ; Anaesthetized rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1.) The purpose of this study was to investigate the role of neuronal uptake in the appearance in plasma of the primary noradrenaline metabolite 3,4-dihydroxyphenylglycol (DOPEG). To this end, steady-state changes in mixed central-venous plasma concentrations of noradrenaline and DOPEG produced by noradrenaline infusions or by changes in sympathetic tone were determined in anaesthetized rabbits either under control conditions or after treatment with desipramine (2 mg kg−1). The steady-state kinetics of infused DOPEG were also evaluated. (2.) Infused DOPEG (2.9 nmol kg−1 min−1 i.v. for 75 min) reached steady-state concentrations in plasma within less than 30 min, disappeared from plasma with a half-life of 2.3 min and showed a total-body plasma clearance of 84.0 ml kg−1 min−1 (3.) Constant-rate infusions of noradrenaline (1.2–5.9 nmol kg−1). (min−1 i.v. for 75 min) produced increases in plasma noradrenaline and DOPEG concentrations which were linearly related to the rate of noradrenaline infusion. Thus, the plasma clearance of infused noradrenaline (75.8 ml kg−1). min−1 as well as the increase in plasma DOPEG expressed in % of that in plasma noradrenaline (9.4%) was virtually independent of the noradrenaline infusion rate. (4.) Desipramine reduced the plasma clearance of infused noradrenaline by 35.4% and the increment in plasma DOPEG relative to that in plasma noradrenaline by 75.3%. From these results and the plasma clearance of noradrenaline and DOPEG it was calculated that the rate at which presynaptically formed DOPEG appeared in plasma amounted to 7.9% of the rate of total noradrenaline removal and to 22.3% of the rate of neuronal uptake. (5.) The rate of appearance in plasma of DOPEG originating from the neuronal re-uptake of endogenous noradrenaline was 192.3 pmol (kg−1). min−1 suggesting that the rate of neuronal re-uptake amounted to 862.3 pmol (kg−1) min−1 (6.) The slope of the regression line relating plasma DOPEG to plasma noradrenaline concentrations under conditions of noradrenaline release exceeded that of the corresponding regression line observed during noradrenaline infusion by a factor of about 10. This difference in slope suggests that, in the absence of infused noradrenaline, the average noradrenaline concentration at all noradrenergic neuroeffector junctions of the rabbit is 3.2 times as high as that in plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169681
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