CATECHOL-O-METHYLTRANSFERASE INHIBITION INCREASES THE UPTAKE OF C-11 3-(3,4-DIHYDROXYPHENYL)-L-ALANINE IN THE RAT PANCREAS

Background: The objective of the present investigation was to evaluate the uptake and metabolism of 3-(3,4-dihydroxyphenyl-L-alanine) (L-DOP A) in the rat pancreas. Methods: The procedure included intravenous in jection of the positron-emitting radiotracer L-[beta-C-11]DOPA (DOP) i nto unanaesthetized male Sprague-Dawley rats and evaluation of uptake of radioactivity in organs in animals only given the tracer and in ani mals given therapeutic doses of three different catechol-O-methyltrans ferase (COMT) inhibitors, OR-486, OR-611, or Ro 41-0960. Selected panc reatic were homogenized, and the chemical form bearing the radioactivi ty was analysed with high-performance liquid chromatography (HPLC). Re sults: The main finding was that the tracer uptake in the pancreas inc reased fourfold when the rats were pretreated with COMT inhibitors. Ha lf maximum effect of OR-486 was found at a dose of 0.2 mg/kg. HPLC ana lysis showed that with COMT inhibitor, the radioactivity in the pancre as consisted of 90% DOPAC. When administering MAO-A and COMT inhibitor together, the pancreas radioactivity corresponded to dopamine. Also i n the pig pancreas a significant increase of DOP was observed after CO MT inhibition. Conclusions: This study has shown a high turnover of L- DOPA in the rat pancreas, which can be modulated to give enhanced leve ls of DOPAC or dopamine by COMT and MAO inhibition.