Summary
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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.
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2.
Cocaine caused a concentration-dependent inhibition of the rate of deamination; the ID50 was 5.62 μM.
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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.
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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.
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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.
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Trendelenburg, U., Graefe, K.H. & Eckert, E. The prejunctional effect of cocaine on the isolated nictitating membrane of the cat. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 69–82 (1972). https://doi.org/10.1007/BF00505068
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DOI: https://doi.org/10.1007/BF00505068