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Release of Endogenous 3,4-Dihydroxyphenylethylamine and Its Metabolites from the Isolated Neurointermediate Lobe of the Rat Pituitary Gland. Effects of Electrical Stimulation and of Inhibition of Monoamine Oxidase and Reuptake
Authors:Kurt Racké  Erich Muscholl
Institution:Department of Pharmacology, University of Mainz, Mainz, F.R.G.
Abstract:Isolated rat neurointermediate lobes were incubated in vitro. The release of 3,4-dihydroxyphenylethylamine (dopamine, DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and methoxyphenylethanol (MOPET) was determined by HPLC with electrochemical detection. Under resting conditions, the outflow of metabolites was 35-50 times that of DA. HVA accounted for 50%, DOPAC for 45%, and MOPET for 5% of the metabolites. Although an equivalent of 40-50% of the tissue DA content was released per hour as metabolites, the tissue DA content was not reduced after 110 min of incubation. The spontaneous outflow of DA and its metabolites was not affected by the DA uptake inhibitor GBR 12921 (100 nM). Pargyline (10 microM) caused a time-dependent decrease of all metabolites (up to 90%). In the presence of GBR 12921 and pargyline, the spontaneous outflow of DA increased sevenfold. Removal of the intermediate lobe caused a 78% reduction in tissue DA content and a corresponding reduction of the outflow of metabolites. Electrical stimulation of the pituitary stalk (0.2 ms, 10 V, 15 Hz, three times for 1 min at intervals of 1 min) induced an increase in outflow of DA and all metabolites. DA accounted for 15%, HVA for 41%, DOPAC for 32%, and MOPET for 12% of the evoked release. The electrically evoked release of DA increased fourfold in the presence of GBR 12921 or pargyline and the effects of both drugs were additive. The evoked release of metabolites was not significantly affected by GBR 12921 but completely abolished by pargyline. In conclusion, oxidative deamination and O-methylation are important pathways for the catabolism of DA in the neurointermediate lobe.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords:Tuberohypophyseal dopamine  Dopamine metabolites  Dihydroxyphenylacetic acid  Homovanillic acid  Neurointermediate lobe
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