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
    The effect of cocaine on uptake of and sensitivity to noradrenaline in isolated nictitating membranes before and after storage in the cold (1970)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 383-398 
    Details
    ISSN: 1432-1912
    Keywords: Cocaine ; Cold-Stored Tissues ; Neuronal Uptake of Nor-adrenaline ; Nictitating Membrane of Cat ; Supersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Experiments were carried out on fresh isolated cat nictitating membranes as well as on muscles stored in the cold for 7 days. Storage reduced the cocaine-induced supersensitivity to (−)-noradrenaline but did not abolish it it also reduced responses to tyramine, and about halved the noradrenaline content of the tissue. Cocaine failed to potentiate responses of fresh or of stored muscles to the methoxamine (which is not taken up by adrenergic nerves). The incubation with 2.5 ml of 100 ng/ml of (−)-noradrenaline (in the presence of the inhibitor of catechol-O-methyl transferase), fresh muscles removed noradrenaline from the incubation medium at a rate of about 70 ng per gram of tissue per min; 10 Μg/ml of cocaine reduced rate of removal by 81%. Muscles stored in the cold removed less noradrenaline from the medium (about 45 ng/g×min−1) than fresh ones, and cocaine reduced the rate of removal by 56%. The neuronal uptake mechanism of the nictitating membrane does not seem to be stereoselective, since the rate of removal of (+)-noradrenaline from the incubation medium was similar to that of the (−)-isomer. It is concluded that cold storage of the muscle abolishes neither the neuronal uptake of noradrenaline nor the ability of cocaine to impair this uptake; however, both parameters were reduced. Since the sensitizing action of cocaine is similarly reduced, there is no reason to doubt the causal relation between impairment by cocaine of neuronal uptake and ensuing supersensitivity to (−)-noradrenaline.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00997276
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    The prejunctional effect of cocaine on the isolated nictitating membrane of the cat (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 69-82 
    Details
    ISSN: 1432-1912
    Keywords: Cocaine ; Nictitating Membrane ; Uptake Theory ; Inhibition of Uptake ; Supersensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Pairs of smooth muscles isolated from the nictitating membrane of reserpine-pretreated cats were incubated four times with 1.2 ml of Krebs' solution containing 10 ng/ml of 3H-(±)-noradrenaline for 7.5 min each (in the presence of ascorbic acid and EDTA to prevent autoxidation and of U-0521 to block COMT). The appearance of deaminated 3H-catechols in the bath was measured and regarded as a measure of neuronal uptake. 2. Cocaine caused a concentration-dependent inhibition of the rate of deamination; the ID50 was 5.62 μM. 3. Cocaine caused a concentration-dependent increase in responses of the isolated muscles to 0.059 μM (−)-noradrenaline with a maximum increase of about 115 times normal. 4. The results were applied to the model proposed by Maxwell et al. (1966). The agreement between the expected and observed relationship between rate of uptake and degree of supersensitivity was satisfactory. Apparently, the effect of cocaine on the nictitating membrane is predominatly or entirely prejunctional. 5. The results indicate that the true K m for noradrenaline and the true K i for cocaine are considerably smaller than the apparent Km and Ki values obtained with conventional methods.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00505068
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Sodium-dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens (1986)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 334 (1986), S. 397-402 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal noradrenaline carrier ; Inhibition of transport-Na+-dependence ; Desipramine ; Cocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Vasa deferentia obtained from reserpine-pretreated rats were incubated (monoamine oxidase and catechol-O-methyltransferase inhibited) in media containing various concentrations of3H-(−)noradrenaline and Na+ and initial rates of the neuronal uptake of3H-noradrenaline measured both in the absence and presence of uptake inhibitors after 1 min of incubation. 2. When rates of uptake were determined at various3H-noradrenaline (1.0–12.2 μmol/l) and two fixed Na+ concentrations (25 and 140 mmol/l), the inhibition of uptake produced by (+)amphetamine, (−)metaraminol, desipramine, nomifensine and cocaine was competitive with respect to3H-noradrenaline at both Na+ concentrations. While theK i for (+)amphetamine, (−)metaraminol desipramine and nomifensine increased when the Na+ concentration was lowered, that for cocaine decreased. 3. When the Na+ concentration was varied (10–140 mmol/l) and the3H-noradrenaline concentration held constant (1.2 μmol/l), (+)amphetamine, (−)metaraminol, nomifensine and desipramine acted as mixed-type inhibitors with respect to Na+, and the inhibition of uptake produced by these drugs was the more pronounced, the higher the Na+ concentration. On the other hand, cocaine was competitive with Na+ and the inhibition produced by this drug was the more pronounced, the lower the Na+ concentration. 4. It is concluded that the inhibitors of neuronal uptake tested here act in dependence on the external Na+ concentration. Desipramine and nomifensine resemble alternative amine substrates in being more potent at high than at low Na+ concentrations. On the other hand cocaine is more potent at low than at high Na+ concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00569377
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Chloride-dependence of the potency of inhibitors of the neuronal noradrenaline carrier in the rat vas deferens (1989)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 339 (1989), S. 65-70 
    Details
    ISSN: 1432-1912
    Keywords: Cl−-dependence ; Neuronal uptake ; Inhibition of neuronal uptake ; Desipramine ; Cocaine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary (1) Vasa deferentia obtained from reserpine-pretreated rats were exposed to 0.15 μmol 1−1 3H-(−)noradrenaline (with monoamine oxidase and catechol-O-methyltransferase being inhibited) and initial rates of the neuronal 3H-noradrenaline uptake as well as IC50 values for inhibition of uptake by desipramine, cocaine or (−)metaraminol determined at various external Cl− concentrations (0–145 mmol 1−1) and a fixed high Na+ concentration (145 mmoll−1). (2) When the Cl− concentration in the medium was decreased neuronal uptake fell. As far as Cl− concentrations ranging from 10 to 145 mmol 1−1 are concerned, the dependence of uptake on Cl− obeyed Michaelis-Menten kinetics with an apparent K m and V max of 6.2 mmol 1−1 and 116 pmol g−1 min−1, respectively. At Cl− concentrations below 10 mmol l−1, uptake was higher than expected from the values of K m and V max, and even in the nominal absence of Cl− from the medium a remainder of neuronal uptake was still detectable. Evidence is presented to show that, on incubation at Cl− concentrations below 10 mmol l−1, intracelluar Cl− leaks out, so that the actual Cl− concentrations in the extracellular fluid are probably higher than in the medium. (3) The potencies of desipramine and cocaine for inhibition of neuronal uptake were markedly dependent on the Cl− concentration in the medium, but the type of Cl− dependence differed. While the IC50 for desipramine decreased, that for cocaine increased with increasing Cl− concentration (2–145 mmol l−1). The value of IC50 for cocaine and that of 1/IC50 for desipramine approached saturation (with an apparent Hill coefficient of about unity) when plotted against the Cl− concentration; half-maximum values were observed at Cl− concentrations of 9 and 24 mmol l−1, respectively. (4) (−)Metaraminol (an alternative substrate of the noradrenaline carrier) remained equally potent in inhibiting neuronal uptake when the Cl− concentration was decreased from 145 to 2 mmol l−1. However, when Cl− was omitted from the medium, the IC50 for (−)metaraminol increased. Hence, the C−-dependence of the potency of (−)metaraminol appears to be restricted to very low extracellular Cl− concentrations. (5) It is concluded that not only the neuronal uptake process itself, but also its inhibition by desipramine and cocaine are highly Cl−-dependent. Since desipramine and cocaine differ with respect to the type of Cl−-dependence of their inhibitory potency, they are likely to act by combining with distinctly different states of the noradrenaline carrier. It is suggested that desipramine interacts with the carrier loaded with Cl− while cocaine is capable of interacting with its Cl−-free state.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00165128
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    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
  • 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 contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines (1996)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 193-199 
    Details
    ISSN: 1432-1912
    Keywords: Key words Noradrenaline ; Adrenaline ; Dopamine ; Total-body plasma clearance ; Pulmonary plasma clearance ; MAO inhibition ; COMT inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To study the effects of inhibition of catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) on the removal of circulating catecholamines, anaesthetized rabbits were infused for 120 min with 3H-labelled noradrenaline, adrenaline and dopamine. Total-body plasma clearances (Cltot) and pulmonary fractional extractions (ERp) of the infused amines and the cardiac output of plasma (COp) were determined under steady-state conditions at the end of each of two consecutive 60-min treatment periods. MAO and COMT were inhibited by treatment with pargyline (40 mg/kg) and tolcapone (3 mg/kg followed by 1.5 mg/kg given every 30 min), respectively. Two groups of animals were studied. Group I involved animals treated with tolcapone throughout and given pargyline at the beginning of the second treatment period. In group II, pargyline was given at the beginning of the first, and the treatment with tolcapone was started at the beginning of the second treatment period. As previous experiments had shown that COMT inhibition alone is without any effect on Cltot of the three catecholamines considered here, the results obtained in the first treatment period of group I can be taken to reflect control results. At the end of the first treatment period, Cltot of noradrenaline, adrenaline and dopamine (expressed as a percentage of COp) was 88%, 85% and 142%, respectively, in group I (COMT inhibition) and 67%, 77% and 115%, respectively, in group II (MAO inhibition; P〈0.05 for the group difference regarding Cltot of noradrenaline and dopamine). MAO inhibition on top of COMT inhibition (group I) lowered Cltot of noradrenaline, adrenaline and dopamine by 23%, 12% and 26%, respectively, and COMT inhibition on top of MAO inhibition (group II) reduced Cltot of these catecholamines by 13%, 20% and 17%, respectively. At the end of the first treatment period, the pulmonary plasma clearance (Clp=ERp×COp) of noradrenaline and dopamine was 13 and 25 ml kg-1 min-1, respectively, in group I and 12 and 28 ml kg-1 min-1, respectively, in group II. Clp of adrenaline did not differ from zero in either group. Clp of noradrenaline and dopamine was reduced by 74% and 70%, respectively, when both enzymes were inhibited in group I and by 70% and 67%, respectively, when both enzymes were inhibited in group II. Hence, inhibition of either MAO or COMT alone had little, if any, effect on the removal of noradrenaline, adrenaline and dopamine on passage through the systemic and pulmonary circulation. Combined inhibition of both MAO and COMT was highly effective in reducing the pulmonary clearance of noradrenaline and dopamine, but produced only minor decreases in the total-body clearance of all three catecholamines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00168757
    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
    Saturation kinetics of the adrenergic neurone uptake system in the perfused rabbit heart. A new method for determination of initial rates of amine uptake (1978)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 302 (1978), S. 263-273 
    Details
    ISSN: 1432-1912
    Keywords: Neuronal uptake ; Initial rates of amine uptake ; Lag period for amine uptake ; Cocaine ; Rabbit heart
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Hearts were obtained from normal or reserpine-pretreated rabbits and perfused at a constant rate (3.6 ml·g−1·min−1) with Tyrode's solution containing 14C- or 3H-sorbitol and various concentrations of 3H-(−)noradrenaline (NA), 14C-(+)NA or 3H-(±)metaraminol; when NA was used, monoamine oxidase and catechol-O-methyl transferase were inhibited. During perfusion for 2 min the arterio-venous difference for 3H and 14C activity (and in this way the removal of amine and sorbitol from the perfusion fluid) was determined at intervals of 5 s. The uptake of amine into intracellular spaces of the heart was obtained by subtraction of the removal of sorbitol from that of amine; it was cumulatively added and plotted against time (uptake curve). Uptake was overwhelmingly neuronal. 2. The uptake curves were sigmoidal: after a brief initial lag period, uptake curves became linear; there-after, the slope of the curves decreased. The last phase of divergence from linearity occurred the earlier and was the more pronounced, the higher the amine concentration. It was interpreted to indicate that neuronal efflux of amine then began to reduce net uptake. 3. From the slope of the linear phase of the uptake curves initial rates of amine transport were obtained. They were saturable with increasing amine concentrations and obeyed Michaelis-Menten kinetics. The apparent K m values of the three amines were similar in magnitude and ranged from 2.9 to 5.9 μM. Uptake was stereoselective in that the V max of (+)NA was significantly lower than that of (−)NA. Pretreatment with reserpine affected neither the K m nor the V max for uptake. Cocaine was a potent competitive inhibitor of amine transport (K i=0.5–1.0 μM). 4. The intercept of the linear phase of the uptake curves on the time axis (t lag) (corrected for the time necessary for transit through the dead space) was taken as a measure of the lag period. It declined when uptake was progressively saturated (or inhibited) by increasing substrate (or cocaine) concentrations. Moreover, t lag was always linearly correlated with the fraction of amine removed from the perfusion fluid. These findings indicate that the equilibration of the uptake sites with the substrate concentration in the perfusion fluid is delayed by the uptake process itself, especially under low saturation conditions (i.e., when S〈K m).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508295
    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...