Catechol-O-methyltransferase inhibition increases the uptake of 11C-3-(3,4-dihydroxyphenyl)-L-alanine in the rat pancreas

Scandinavian Journal of Gastroenterology
M BergströmB Långström

Abstract

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. 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). 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. This study has shown a high turnover of L-DOPA in the rat pancreas, which...Continue Reading

References

May 1, 1990·Journal of Computer Assisted Tomography·E Rota KopsL E Feinendegen
May 1, 1995·Radiology·H AhlströmK Oberg
Aug 1, 1994·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·T KarhunenP Panula
May 1, 1993·Gastroenterology·L KnutsonG Flemström

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Citations

Mar 3, 2012·American Journal of Respiratory and Critical Care Medicine·Tim LahmIrina Petrache
Nov 13, 2013·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Teemu KalliokoskiMerja Haaparanta-Solin

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