Central noradrenergic activity and the formation of glycol sulfate metabolites of brain norepinephrine |
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Authors: | Eric A. Stone |
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Affiliation: | Millhauser Laboratories of the Department of Psychiatry New York University Medical Center New York, NY 10016, USA |
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Abstract: | The present study utilized intraventricular injection of Na235SO4 to detect drug induced changes in the formation of the two major metabolites of rat brain norepinephrine (NE) - the sulfate conjugates of 3-methoxy-4-hydroxyphenylglycol (MOPEG-SO4) and 3,4-dihyd (DOPEG-SO4). Assays involved the hypothalamus only. Rats pretreated with clonidine showed a reduced formation of both MOPEG-35SO4 and DOPEG-35SO4 after intraventricular Na235SO4 as well as reduced synthesis of 3H-NE from intraventricular 3H-tyrosine. Phenoxybenzamine (POB) produced increases in the synthesis of both 35S-labeled conjugates and 3H-NE. Neither drug altered the loss of exogenous 3H-MOPEG-SO4 but clonidine increased both the accumulation of labeled sulfate and the sulfation of exogenous MOPEG in pheniprazine treated rats. These results show that the rates of formation of the labeled glycol sulfates are sensitive indicators of changes in brain NE turnover but can also be influenced by factors involved in sulfation that are unrelated to NE turnover. Blockade of NE synthesis with alpha methyltyrosine did not affect resting or POB-elevated levels of the labeled conjugates until stores of NE were reduced by 40%. The latter findings suggest that central noradrenergic neurons can release and metabolize NE at a normal rate despite synthesis blockade so long as adequate stores of NE are available. |
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