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Catechol-O-Methyltransferase Inhibition Increases the Uptake of 11C-3-(3,4-Dihydroxyphenyl)-L-Alanine in the Rat PancreasRead
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. (Endokrin tumörbiologi)
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1996 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 31, no 12, p. 1216-1222Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

The objective of the present investigation was to evaluate the uptake and metabolism of 3-(3,4-dihydroxyphenyl-L-alanine) (L-DOPA) in the rat pancreas.

METHODS:

The procedure included intravenous injection of the positron-emitting radiotracer L-[beta-11C] DOPA (DOP) into unanaesthetized male Sprague-Dawley rats and evaluation of uptake of radioactivity in organs in animals only given the tracer and in animals given therapeutic doses of three different catechol-O-methyltransferase (COMT) inhibitors, OR-486, OR-611, or Ro 41-0960. Selected pancreati were homogenized, and the chemical form bearing the radioactivity was analysed with high-performance liquid chromatography (HPLC).

RESULTS:

The main finding was that the tracer uptake in the pancreas increased fourfold when the rats were pretreated with COMT inhibitors. Half maximum effect of OR-486 was found at a dose of 0.2 mg/kg. HPLC analysis showed that with COMT inhibitor, the radioactivity in the pancreas consisted of 90% DOPAC. When administering MAO-A and COMT inhibitor together, the pancreas radioactivity corresponded to dopamine. Also in the pig pancreas a significant increase of DOP was observed after COMT inhibition.

CONCLUSIONS:

This study has shown a high turnover of L-DOPA in the rat pancreas, which can be modulated to give enhanced levels of DOPAC or dopamine by COMT and MAO inhibition.

Place, publisher, year, edition, pages
1996. Vol. 31, no 12, p. 1216-1222
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-149760PubMedID: 8976015OAI: oai:DiVA.org:uu-149760DiVA, id: diva2:405506
Available from: 2011-03-22 Created: 2011-03-22 Last updated: 2017-12-11Bibliographically approved

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