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ACCUMULATION AND METABOLISM OF NOREPINE‐PHRINE IN RAT HYPOTHALAMUS AFTER EXHAUSTIVE STRESS 1
Author(s) -
Stone E. A.
Publication year - 1973
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1973.tb06004.x
Subject(s) - reserpine , medicine , metabolism , endocrinology , chemistry , hypothalamus , endogeny , norepinephrine , metabolite , dopamine , biology
—Exhaustive stress in rats is followed by a temporary reduction of hypothalamic norepinephrine (NE) together with a persistent increase in turnover during recovery. To test for persistent alterations of NE storage and metabolism produced by stress, rats were subjected to 3 h of forced running and were then injected intraventricularly with [ 3 H]NE or [ 3 H]dopamine (DA). The hypothalamus was assayed for [ 3 H]NE and its metabolites at various intervals after injection. The effects of stress were compared with those of reserpine (7·5 mg/kg) or α‐methyltyrosine (AMT, 300 mg/kg) pretreatment. It was found that the stress‐induced reduction of endogenous NE was not accompanied by a change in the accumulation of exogenous [ 3 H]NE either 10 or 30 min after injection, whereas the NE depletions produced by reserpine or AMT were associated with decreased or increased accumulation, respectively. However, stress did produce an increased accumulation of [ 3 H]NE endogenously synthesized from [ 3 H]DA. These results indicate that exhaustive stress does not adversely affect the storage of NE. They also suggest that stores of NE depleted by stress are replenished chiefly with newly synthesized NE and not through an increased uptake and binding or decreased metabolism of extraneuronal NE. The latter factors may play a role in the maintenance of brain NE stores when biosynthesis is low, i.e. after AMT. The major metabolites of exogenous [ 3 H]NE, at 30 min after injection, were identified as conjugates of 3,4‐dihydroxyphenylglycol (DOPEG) and 3‐methoxy‐4‐hydroxyphenylglycol (MOPEG) in approximately equal amounts. The finding of high levels of conjugated DOPEG confirms a recent report (S lgden and E ccleston , 1971) that this compound is a major metabolite of brain NE. Reserpine produced marked elevations of both conjugates; AMT slightly reduced each. Prior stress increased only conjugated MOPEG, an observation suggesting that CNS levels of this metabolite may reflect NE released by nervous activity.

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