Bergström M, Lu L, Marquez M, Moulder R, Jacobsson G, Ogren M, Eriksson B, Watanabe Y, Långström B
Subfemtomole Biorecognition Project, Uppsala University, Sweden.
Scand J Gastroenterol. 1996 Dec;31(12):1216-22. doi: 10.3109/00365529609036913.
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 can be modulated to give enhanced levels of DOPAC or dopamine by COMT and MAO inhibition.
本研究的目的是评估3-(3,4-二羟基苯-L-丙氨酸)(L-DOPA)在大鼠胰腺中的摄取和代谢。
该实验过程包括对未麻醉的雄性斯普拉格-道利大鼠静脉注射正电子发射放射性示踪剂L-[β-11C]多巴(DOP)，并评估仅给予示踪剂的动物以及给予三种不同儿茶酚-O-甲基转移酶(COMT)抑制剂OR-486、OR-611或Ro 41-0960治疗剂量的动物体内各器官放射性的摄取情况。选取胰腺进行匀浆，并用高效液相色谱(HPLC)分析带有放射性的化学形式。
主要发现是，当大鼠用COMT抑制剂预处理时，胰腺中的示踪剂摄取增加了四倍。发现OR-486在剂量为0.2 mg/kg时达到半数最大效应。HPLC分析表明，使用COMT抑制剂时，胰腺中的放射性由90%的3,4-二羟基苯乙酸(DOPAC)组成。当同时给予单胺氧化酶A(MAO-A)和COMT抑制剂时，胰腺放射性对应于多巴胺。在猪胰腺中，COMT抑制后也观察到DOP显著增加。
本研究表明大鼠胰腺中L-DOPA的周转率很高，通过抑制COMT和MAO可以调节其水平，使DOPAC或多巴胺水平升高。
