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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 383-398 
    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
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 45-68 
    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
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