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Journal of Pharmacology and Experimental Therapeutics

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Research Article

EFFECTS OF DESMETHYLIMIPRAMINE AND COCAINE ON THE UPTAKE, RETENTION AND METABOLISM OF H3-TYRAMINE IN RAT BRAiN SLICES

M. I. STEINBERG and C. B. SMITH
Journal of Pharmacology and Experimental Therapeutics May 1970, 173 (1) 176-192;
M. I. STEINBERG
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C. B. SMITH
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Abstract

Slices of hypothalamus, brainstem, parietal cortex and caudate from rat brain were incubated in Krebs-Ringer solution at 37°C for 20 minutes with H3- tyramine (1.4 x 10-7 M). Slices from all areas synthesized H3-p-hydroxyphenylacetic acid (H3-p-HPAA) and H3-octopamine. In addition, some of the H3-tyramine which was taken up was retained unmetabolized. Although caudate slices made less H3-octopamine, these slices made more H3-p-HPAA and retained much more H3-tyramine than slices from the other areas. Neither H3-octopamine nor H3-p-hydroxymande1ic acid was found in bathing solutions or washes of slices from any area. Cocaine (10-6-3 x 10-4 M), when added to the incubation flask 15 minutes before the addition of H3-tyramine, caused a decrease in both H3-octopamine and H3-p-HPAA synthesis as well as a decrease in the amount of H3- tyramine retained. In contrast, desmethylimipramine (DMI, 10-7 and 10-6 M), when added to the incubation flask 15 minutes before the H3-tyramine, caused a marked decrease in the synthesis of H3-octopamine but did not decrease the synthesis of H3-p-HPAA or diminish the retention of H3-tyramine. Similar results were obtained with slices from rats pretreated with DMI (2-60 mg/kg, i.p.) one hour before sacrifice. The inhibition of H3-octopamine synthesis caused by DMI, both in vivo and in vitro, was noncompetitive, whereas that produced by cocaine was competitive. Cocaine (10-4 M) and DMI (60 mg/ kg and 10-6 M), when added to homogenates of hypothalamus, had no effect on the synthesis of either H3-p-hydroxymandelic acid or 3-p-HPAA. These results indicate that cocaine blocks the uptake of H3-tyramine at the neuronal membrane. In contrast, low doses of DMI do not prevent the uptake of H3-tyramine at the neuronal membrane and subsequent synthesis of H3-p-HPAA, but do prevent the uptake of H3-tyramine into the intraneuronal sites where it is converted into H3-octopamine.

Footnotes

    • Received June 5, 1969.
    • Accepted January 17, 1970.
  • © 1970, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 173, Issue 1
1 May 1970
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Research Article

EFFECTS OF DESMETHYLIMIPRAMINE AND COCAINE ON THE UPTAKE, RETENTION AND METABOLISM OF H3-TYRAMINE IN RAT BRAiN SLICES

M. I. STEINBERG and C. B. SMITH
Journal of Pharmacology and Experimental Therapeutics May 1, 1970, 173 (1) 176-192;

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Research Article

EFFECTS OF DESMETHYLIMIPRAMINE AND COCAINE ON THE UPTAKE, RETENTION AND METABOLISM OF H3-TYRAMINE IN RAT BRAiN SLICES

M. I. STEINBERG and C. B. SMITH
Journal of Pharmacology and Experimental Therapeutics May 1, 1970, 173 (1) 176-192;
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