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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 267 (1970), S. 383-398 
    ISSN: 1432-1912
    Schlagwort(e): Cocaine ; Cold-Stored Tissues ; Neuronal Uptake of Nor-adrenaline ; Nictitating Membrane of Cat ; Supersensitivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 69-82 
    ISSN: 1432-1912
    Schlagwort(e): Cocaine ; Nictitating Membrane ; Uptake Theory ; Inhibition of Uptake ; Supersensitivity
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: 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.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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