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Journal of Pharmacology And Experimental Therapeutics, Vol. 144, Issue 1, 66-75, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics


THE TURNOVER OF ENDOGENOUSLY LABELED CATECHOLAMINE IN SEVERAL REGIONS OF THE SYMPATHETIC NERVOUS SYSTEM

W. R. Burack 1 and P. R. Draskóczy 1

1 Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The rate of turnover of radioactive catecholamine in several regions of the sympathetic nervous system of mice has been measured by a technique involving endogenous labeling. Catecholamine storage sites were labeled by the intravenous administration of radioactive dopa or tyrosine, both precursors of catecholamine, in amounts insufficient to cause measurable change in the catecholamine content of the tissues under study. The subsequent fall in specific activity served as an index of the rate of turnover.

Conversion of DL-dopa-H3 into catecholamine proceeded very quickly; 4 hours after it had been injected, dopa-H3 had practically disappeared from blood and tissues and nearly all of the labeled catecholamine in the brain, heart, liver and adrenal gland was norepinephrine and/or epinephrine.

Specific activity of catecholamine in each organ was determined at intervals up to 4 days. In brain, liver and heart specific activity fell steeply at first (tfrac12 = 4 to 8 hours) then gressively more slowly so that after 24 hours tfrac12 = 18 hours. This implies either that the labeled catecholamine was distributed in more than one pool, each of which was turning over at a different rate and/or that catecholamine stores were nonhomogeneously labeled. In adrenal glands specific activity of catecholamine either rose or did not change during the first 8 hours after dopa-H3 was injected, probably because circulating catecholamine of high specific activity was being taken up and stored. From 8 hours to 3 days specific activity fell at a disappearance half-time of about 1 week.

The disappearance curve for spleen may not for the first 6 hours be taken to represent change in specific activity of beta-bydroxylated catecholamine. However, after this time the specific activity diminished with a tfrac12 of approximately 24 hours.

When C14- or H3-tyrosine was given intravenously as precursor, catecholamine in brain was more heavily labeled than in any of the other organs which were studied. The rate of fall of specific activity in the adrenal medulla closely resembled that observed when labeling was with dopa-H3. The disappearance curves for heart, liver and brain lacked an initial rapid fall but after 24 hours the slopes were similar to those found when dopa-H3 was used as precursor.

Submitted on August 27, 1962
Accepted on November 27, 1963




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J. J. Schildkraut, P. R. Draskoczy, and P. S. Lo
Norepinephrine Pools in Rat Brain: Differences in Turnover Rates and Pathways of Metabolism
Science, May 7, 1971; 172(3983): 587 - 589.
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Arch Neurol, January 1, 1970; 22(1): 31 - 39.
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Copyright © 1964 by the American Society for Pharmacology and Experimental Therapeutics.