title: Catechol-O-methyltransferase inhibition increases the uptake of 11C-3-(3,4-dihydroxyphenyl)-L-alanine in the rat pancreas.
abstract: 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.
authors.affiliation: Subfemtomole Biorecognition Project, Uppsala University, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Bergström
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Marquez
authors.forename: R
authors.initials: R
authors.lastname: Moulder
authors.forename: G
authors.initials: G
authors.lastname: Jacobsson
authors.forename: M
authors.initials: M
authors.lastname: Ogren
authors.forename: B
authors.initials: B
authors.lastname: Eriksson
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: B
authors.initials: B
authors.lastname: Långström
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001577:Benzophenones / Q000008:administration & dosage / Q000494:pharmacology*; D002394:Catechol O-Methyltransferase / Q000008:administration & dosage / Q000494:pharmacology; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D007980:Levodopa / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D009570:Nitriles; D010179:Pancreas / Q000187:drug effects*; D011849:Radioactive Tracers; D051381:Rats; D017207:Rats, Sprague-Dawley; D014055:Tomography, Emission-Computed
chemical_list: D001577:Benzophenones; D002396:Catechols; D004791:Enzyme Inhibitors; D009570:Nitriles; D011849:Radioactive Tracers; C071721:Ro 41-0960; D007980:Levodopa; C071192:entacapone; D002394:Catechol O-Methyltransferase; C057726:OR486