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.
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with the Technical Assistance of Miss Roneen D. Hobbs
Part of this work was supported by the Deutsche Forschungsgemeinschaft.
The authors gratefully acknowledge the excellent technical assistance of Miss Helga Damm. We are grateful to Dr. E. A. Maxwell of Burroughs Wellcome and Co., Tuckahoe, N.Y.,for the methoxamine, to Dr. A. J. Plummer of CIBA Pharmaceutical Products, Inc., Summit, N.J., for the reserpine, and to Dr. G. A. Johnson of Upjohn Comp., Kalamazoo, Mich. for the U-0521.
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Graefe, K.H., Trendelenburg, U. The effect of cocaine on uptake of and sensitivity to noradrenaline in isolated nictitating membranes before and after storage in the cold. Naunyn-Schmiedebergs Arch. Pharmak. 267, 383–398 (1970). https://doi.org/10.1007/BF00997276
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DOI: https://doi.org/10.1007/BF00997276