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
  • 1
    Electronic Resource
    Electronic Resource
    On the stereoselectivity of the neuronal uptake in the cat's nictitating membrane (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 45-68 
    Details
    ISSN: 1432-1912
    Keywords: Stereoselectivity of Uptake ; Noradrenaline ; Neuronal Uptake ; Neuronal Deamination ; Nictitating Membrane
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Pairs of smooth muscles isolated from the nictitating membrane of the cat were incubated with 1.2 ml of Krebs' solution containing 10 ng/ml of 3H-(±)-noradrenaline for 7.5 min (in the presence of U-0521 to inhibit COMT). Removal of the amine from the bath as well as the appearance of deaminated 3H-catechols in the bath were measured. 2. Pretreatment with reserpine did not affect the rate of removal, while increasing the rate of deamination. The ability of the muscles to retain exogenous amine for one hour was reduced to 12% of normal. 3. A certain fraction of the total production of deaminated 3H-catechols escaped into the medium. For any given duration of incubation this fraction was independent of the concentration of noradrenaline in the medium. On repeated incubation the fraction remained constant. Therefore, reliable estimates of the rate of deamination were obtained with repeated incubations of the same muscle. 4. Sympathetic denervation and/or cocaine revealed that 60% of removal (of which 10% are due to dilution) and 25% of deamination are extraneuronal. 5. For incubations of 7.5 min measured rates of deamination represent initial rates, measured rates of removal do not. 6. Unlabelled (−)- and (+)-noradrenaline were equipotent (ID50=about 1 μM) in inhibiting the deamination of 10 ng/ml of 3H-(±)-noradrenaline. This inhibitory effect must be exerted on neuronal deamination, since extraneuronal deamination (in denervated muscles) was not affected by the addition of unlabelled isomers. 7. It is proposed that, under these experimental conditions, neuronal unptake is the rate limiting step for neuronal deamination, and that neuronal uptake in the cat's nictitating membrane lacks stereoselectivity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505067
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Early intraneuronal mobilization and deamination of noradrenaline during global ischemia in the isolated perfused rat heart (1987)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 336 (1987), S. 508-518 
    Details
    ISSN: 1432-1912
    Keywords: Myocardial ischemia ; Noradrenaline ; Amine carrier ; Noradrenaline metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Isolated rat hearts were perfused according to the Langendorff technique and both extraneuronal uptake of noradrenaline and COMT were inhibited. The noradrenergic neurones were first prelabelled with 3H-(−)-noradrenaline (13 nmol/1). Thereafter the hearts were submitted to global ischemia (perfusion rate reduced from 5 up to 0.5 ml/min) for 60 min and subsequently reperfused for 5 min. The coronary effluent was continuously collected and analyzed for the appearance of 3H-noradrenaline and its metabolites. 1. Global ischemia was associated with an early release of 3H-noradrenaline. At reperfusion a brisk increase in the FRL of 3H-noradrenaline was observed which may indicate that, on severe restriction in coronary flow, perfusion of the tissue became heterogenous and thus partially masked the amount of 3H-noradrenaline released from the noradrenergic nerve terminals. Gradual reduction in coronary flow also progressively reduced (but did not abolish) the total formation of 3H-DOPEG. 2. The maximal efflux of 3H-noradrenaline was observed during the 1st min of reperfusion whereafter the efflux declined rapidly, indicating a wash-out of transmitter trapped in the extracellular space. The efflux of the lipophilic metabolite 3H-DOPEG, on the other hand, continuously increased during the reperfusion. This was due to both new formation and “wash-out” of 3H-DOPEG retained and/or distributed into the tissue during the period of restricted flow. 3. Neither a reduction of the extracellular calcium concentration (from 2.6 mmol/l to 0.1 mmol/1) nor the presence of the calcium entry blocker verapamil (250 nmol/l) reduced the efflux of 3H-noradrenaline seen during ischemia and reperfusion. 4. Desipramine (100 nmol/l) markedly reduced the ischemia-induced release of 3H-noradrenaline and simultaneously attenuated the formation of 3H-DOPEG. 5. A moderate reduction in the ischemia-induced mobilization of 3H-noradrenaline was seen in hearts perfused with 1μol/l reserpine, whereas the formation of 3H-DOPEG from such hearts was markedly higher than in corresponding controls. Only minor deviations from this pattern was observed when desipramine was present in addition to reserpine. It is concluded that a severe restriction in myocardial perfusion rate is associated with an enhanced net leakage of vesicular noradrenaline. This results in a rise of the free axoplasmic noradrenaline concentration which, in combination with an altered transmembrane sodium gradient, induces an increased local release of noradrenaline partly mediated by a calcium-independent, carrier-mediated outward transport. Desipramine, which inhibits this transport mechanism, may have, in addition to its effect on the membrane carrier, an additional effect in reducing the net leakage of transmitter from storage vesicles. Furthermore, despite severe restriction in coronary flow, and thus oxygen delivery, DOPEG is still formed, possibly as a consequence of the elevated axoplasmic noradrenaline concentration which may in part compensate for a reduced monoamineoxidase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00169307
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    1,1′-Diisopropyl-2,4′-cyanine (disprocynium24), a potent uptake2 blocker, inhibits the renal excretion of catecholamines (1997)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 356 (1997), S. 115-125 
    Details
    ISSN: 1432-1912
    Keywords: Key words Disprocynium24 ; Noradrenaline ; Adrenaline ; Dopamine ; Renal excretion ; Organic cation transport ; Inulin clearance ; Uptake2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,1′-Diisopropyl-2,4′-cyanine (disprocynium24), a potent inhibitor of the extraneuronal monoamine transport system (uptake2), was previously shown to reduce the clearance of catecholamines from plasma not only by blocking uptake2 but presumably also by blocking organic cation transport. To provide more direct evidence for the latter conclusion, the present study was carried out in anaesthetized rabbits. It aimed at determining the effect of disprocynium24 on the renal excretion of catecholamines which is known to be, at least in part, a consequence of organic cation transport in the kidney. To this end, the plasma clearance due to renal excretion (Clu) of endogenous as well as infused 3H-labelled adrenaline, noradrenaline and dopamine was determined for 60-min periods of urine collection in rabbits treated either with disprocynium24 (270 nmol kg-1 i.v followed by i.v. infusion of 80 nmol kg-1 min-1) or vehicle. Two groups of animals were studied: group I (monoamine oxidase and catechol-O-methyltransferase intact) and group II (monoamine oxidase and catechol-O-methyltransferase inhibited). A third group of animals with intact monoamine oxidase and catechol-O-methyltransferase was used to study the effect of disprocynium24 on the glomerular filtration rate (as determined by measuring the plasma clearance of inulin). In vehicle controls, Clu of endogenous adrenaline, noradrenaline and dopamine was 7.2, 5.2 and 153.6 ml kg-1 min-1, respectively, in group I and 10.4, 7.0 and 134.3 ml kg-1 min-1, respectively, in group II. Similar control values of Clu were obtained for infused 3H-adrenaline and 3H-noradrenaline, but not for infused 3H-dopamine; Clu of 3H-dopamine (4.9 ml kg-1 min-1 in group I and 15.4 ml kg-1 min-1 in group II) was considerably smaller than Clu of endogenous dopamine, indicating that most of the dopamine in urine (i.e., 98% in group I and 92% in group II) was derived from the kidneys rather than from the circulation. By contrast, only about one quarter of the noradrenaline in urine (32% in group I and 24% in group II) and none of the urinary adrenaline were of renal origin. In both groups, disprocynium24 markedly reduced the Clu of endogenous catecholamines (by 72-90%) and of infused 3H-catecholamines (by 49-69%). Moreover, it preferentially inhibited the renal excretion of those components of urinary dopamine and noradrenaline which were derived from the kidney. Therefore, disprocynium24 inhibits the tubular secretion of catecholamines and, hence, organic cation transport in the kidney. This conclusion was substantiated by the observation that disprocynium24 did not alter the glomerular filtration rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005018
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    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
    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 heterogeneity of the neuronal distribution of exogenous noradrenaline in the rat vas deferens (1990)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 342 (1990), S. 160-170 
    Details
    ISSN: 1432-1912
    Keywords: Rat vas deferens ; Heterogeneous labelling ; 3H-noradrenaline ; Desipramine ; Inhibition of vesicular uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary After loading of the incubated rat vas deferens with 0.2 μmol/l 3H-noradrenaline (followed by 100 min of wash-out with amine-free solution), the efflux of endogenous and exogenous compounds was determined by HPLC with electrochemical detection and by column chromatography with scintillation counting. Two different types of heterogeneity of labelling were found. The first one is due to the preferential labelling of varicosities close to the surface of the tissue, the second one to the preferential labelling of vesicles close to the surface of loaded varicosities. As diffusion distances within the tissue and within varicosities are then longer for endogenous than for exogenous amine and metabolites, the composition of spontaneous efflux of exogenous compounds differed from that for endogenous compounds. Because of preferential neuronal and vesicular re-uptake of endogenous noradrenaline, the percentage contribution by noradrenaline to overall efflux was: endogenous 〈 exogenous. While 3H-DOPEG was the predominant exogenous metabolite, DOPEG and MOPEG equally contributed to the “endogenous” efflux. Desipramine abolished the consequences of the first heterogeneity of labelling, i.e., it increased the efflux more for endogenous than for exogenous noradrenaline; moreover it decreased the efflux of 3H-DOPEG, but increased that of 3H-MOPEG. The reserpine-like compound Ro 41284, on the other hand, abolished the consequences of the second type of heterogeneity; it reduced the specific activity of “total efflux” (i.e., of the sum of noradrenaline + DOPEG + MOPEG) to the specific activity of the tissue noradrenaline. The degree of heterogeneity of labelling was reduced after inhibition of monoamine oxidase and also when the tissues were loaded with 2 or 20 μmol/l 3H-noradrenaline. It is proposed that the various “compartments” and “pools” of noradrenaline described in the literature reflect the two heterogeneities described here.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00166959
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and α1-adrenoceptor antagonistic properties of two cyanine-type inhibitors of extraneuronal monoamine transport (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 268-274 
    Details
    ISSN: 1432-1912
    Keywords: Key wordsα1-Adrenoceptor ; Decynium22 ; Disprocynium24 ; Extraneuronal monoamine transporter ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,1′-Diethyl-2,2′-cyanine (decynium22) and 1,1′-diisopropyl-2,4′-cyanine (disprocynium24) are highly potent inhibitors of the extraneuronal monoamine transporter. When given as i.v. bolus injections (4 μmol kg–1) to anaesthetized rabbits, both drugs elicited a transient fall in blood pressure without altering heart rate. The observed maximum fall in diastolic blood pressure was 59% after decynium22 and 43% after disprocynium24 administration. The pharmacokinetics of decynium22 and disprocynium24 were similar; they were characterized by short half-lives for elimination (8.2 and 4.5 min, respectively) and very high plasma clearances (173 and 180 ml kg–1 min–1, respectively). The mechanism underlying the blood pressure-lowering effect of decynium22 was explored in the isolated incubated rabbit aorta. Decynium22 antagonized the noradrenaline-induced contraction; the pA2 for this interaction was 7.6, and the slope of the corresponding Schild plot was unity. In a membrane preparation from rat myocardium, decynium22 as well as disprocynium24 inhibited the specific binding of [125I]-2-[β-(4-hydroxy-3-iodophenyl)-ethylaminomethyl]-tetralone (125I-HEAT), a selective ligand to α1-adrenoceptors. The Ki‘s were 5.3 and 240 nmol l–1 for decynium22 and disprocynium24, respectively. The type of binding inhibition by decynium22 was competitive. It is concluded that the two inhibitors of extraneuronal monoamine transport decynium22 and disprocynium24 lower blood pressure by blocking α1-adrenoceptors. A comparison of their potencies in blocking extraneuronal monoamine transport and α1-adrenoceptors clearly indicates that disprocynium24 is more suitable for studies designed to determine the role of extraneuronal monoamine transport in vivo. Considering its very fast elimination kinetics, disprocynium24 must be administered by constant rate-infusions in order to avoid large fluctuations of plasma levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171057
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and α1-adrenoceptor antagonistic properties of two cyanine-type inhibitors of extraneuronal monoamine transport (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 268-274 
    Details
    ISSN: 1432-1912
    Keywords: α1-Adrenoceptor ; Decynium22 ; Disprocynium24 ; Extraneuronal monoamine transporter ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1,1′-Diethyl-2,2′-cyanine (decynium22) and 1,1′-diisopropyl-2,4′-cyanine (disprocynium24) are highly potent inhibitors of the extraneuronal monoamine transporter. When given as i.v. bolus injections (4 μmol kg−1) to anaesthetized rabbits, both drugs elicited a transient fall in blood pressure without altering heart rate. The observed maximum fall in diastolic blood pressure was 59% after decynium22 and 43% after disprocynium24 administration. The pharmacokinetics of decynium22 and disprocynium24 were similar; they were characterized by short half-lives for elimination (8.2 and 4.5 min, respectively) and very high plasma clearances (173 and 180 ml kg−1 min−1, respectively). The mechanism underlying the blood pressure-lowering effect of decynium22 was explored in the isolated incubated rabbit aorta. Decynium22 antagonized the noradrenaline-induced contraction; the pA2 for this interaction was 7.6, and the slope of the corresponding Schild plot was unity. In a membrane preparation from rat myocardium, decynium22 as well as disprocynium24 inhibited the specific binding of [125I]-2-[β-(4-hydroxy-3-iodophenyl)-ethy-laminomethyl]-tetralone (125I-HEAT), a selective ligand to α1-adrenoceptors. The Ki's were 5.3 and 240 nmol l−1 for decynium22 and disprocynium24, respectively. The type of binding inhibition by decynium22 was competitive. It is concluded that the two inhibitors of extraneuronal monoamine transport decynium22 and disprocynium24 lower blood pressure by blocking α1-adrenoceptors. A comparison of their potencies in blocking extraneuronal monoamine transport and α1-adrenoceptors clearly indicates that disprocynium24 is more suitable for studies designed to determine the role of extraneuronal monoamine transport in vivo. Considering its very fast elimination kinetics, disprocynium24 must be administered by constant rate-infusions in order to avoid large fluctuations of plasma levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171057
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 275-286 
    Details
    ISSN: 1432-1912
    Keywords: Key words Plasma clearance of catecholamines ; MAO-inhibition ; COMT-inhibition ; Disprocynium24 ; Uptake2 ; Organic cation transporters
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract As selective inhibitors of the extraneuronal monoamine uptake system (uptake2) suitable for in-vivo studies were not available, the question of whether uptake2 plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1′-diisopropyl-2,4′-cyanine iodide (disprocynium24), a novel agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were infused with 3H-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle. Four groups of animals were studied: group I, no further treatment; group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1) inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg–1 i.v. followed by an i.v. infusion of 80 nmol kg–1 min–1) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I 〉 group II 〉 group III 〉 group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29–38% for noradrenaline, 22–31% for adrenaline and 16–22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake1. Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake2, but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00171058
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Stereoselectivity in the metabolism of 3H-noradrenaline during uptake into and efflux from the isolated rat vas deferens (1977)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 299 (1977), S. 225-238 
    Details
    ISSN: 1432-1912
    Keywords: Stereoselective metabolism of noradrenaline ; Neuronal efflux ; Cocaine ; Phenoxybenzamine ; Rat vas deferens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The metabolism of 3H-(-)- and 3H-(±)-noradrenaline (NA) was studied in the isolated rat vas deferens either under conditions of uptake or of efflux of the amine. Any differences obtained between 3H-(-)-and 3H-(±)NA as substrate were interpreted as being a reflection of differences between the two isomers of the amine. 2. Uptake experiments (0.13 μM; 7.5 min) showed that neuronal mechanisms of amine disposition prevail over extraneuronal ones. Thus, most of the metabolites of 3H-NA formed during incubation with the amine (including the O-methylated products) were of neuronal origin. The acid deaminated metabolite 3,4-dihydroxymandelic acid (DOMA), tended to be much better retained by the tissue than the neutral deaminated metabolite, 3,4-dihydroxyphenylethyleneglycol (DOPEG). While neuronal uptake exhibited no stereoselectivity, a pronounced stereoselectivity was found for monoamine oxidase (MAO) [(-)NA〉 (+)NA] as well as for the enzymes which are in series with MAO, namely, aldehyde reductase and aldehyde dehydrogenase [(-)DOPEG〉 (+)DOPEG; (-)DOMA 〈(+)DOMA]. 3. After about 2 h of washout, the efflux of radioactivity from the tissue [which was previously incubated for 30 min with 1.2 μM of either 3H-(-)- or 3H-(±)NA] originated from one neuronal compartment with no stereoselectivity of the rate constant for the efflux of total tritium. The rate-limiting step for the neuronal efflux of tritium resided either in the net efflux of amine from the storage vesicles (normal tissues) or in the net efflux across the axonal membrane (tissues with the amine metabolizing enzymes inhibited). The effects of cocaine and phenoxybenzamine on the neuronal efflux of tritiated compounds strongly depended on the intraneuronal distribution of the 3H-amine. The results indicate that cocaine has only one site of action (neuronal uptake), while phenoxybenzamine exerts reserpine-like as well as cocaine-like effects. 4. The neuronal efflux of tritium from normal tissues preloaded with 3H-(-)- or 3H-(±)NA consisted mainly of amine metabolites (90% of the total; most of this was DOPEG). Since after 2 h of washout the tissue contained hardly any metabolites, these metabolites did not represent pre-formed metabolites (formed during the period of preloading) but newly formed metabolites resulting from the catabolism of the neuronally stored amine. This catabolism was brought about through the activity of presynaptic enzymes and was stereoselective in that more DOPEG, less DOMA and less O-methylated metabolites were formed from (-)-than from (+)NA.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500315
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Choline+: A substrate of the neuronal noradrenaline carrier in the rat vas deferens (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 223-227 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal noradrenaline carrier ; Choline+ ; Accelerative exchange diffusion ; Substitution for Na+ ; Rat vas deferens
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The effects of choline+ (10–40 mmol/l) on 3H-noradrenaline uptake by, and 3H-noradrenaline efflux from, noradrenergic neurones were studied in vasa deferentia of reserpine-pretreated rats at an external Na+ concentration of 100 mmol/l. Monoamine oxidase and catechol-O-methyltransferase were inhibited. 2. Choline+ (20 and 40 mmol/l) competitively inhibited the neuronal uptake of 3H-noradrenaline. From the choline+-induced changes in the apparent Km for 3H-noradrenaline transport, a Ki of 35 mmol/l was obtained. 3. Choline+ (10, 20 and 40 mmol/l) accelerated the neuronal efflux of 3H-noradrenaline in a concentration-dependent manner. This acceleration of efflux was greatly reduced in the presence of 1 μmol/l desipramine, indicating that choline+ is capable of eliciting “accelerative exchange diffusion”. 4. Choline+ (40 mmol/l) and (−)noradrenaline (4.5 μmol/l) (i.e., concentrations about equivalent to the Ki and Km for choline+ and (−)noradrenaline, respectively) produced virtually identical increases in the neuronal efflux of 3H-noradrenaline. 5. Choline+ (3–300 mmol/l) inhibited the specific binding of 3H-desipramine to plasma membranes derived from cultured rat phaeochromocytoma (PC-12) cells. The Ki for this interaction was 48 mmol/l. 6. This results suggest that choline+ acts as alternative substrate of the neuronal noradrenaline transport system and should, therefore, not be used in transport studies with noradrenaline as substitute for Na+ in Na+-deficient media.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508775
    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...