Haubrich D R, Wang P F, Wedeking P W
J Pharmacol Exp Ther. 1975 Apr;193(1):246-55.
The biosynthesis of acetylcholine and the fate of intravenously administered choline [methyl- 3-H] were studied in guinea pigs anesthetized with pentobarbital. Choline and acetylcholine were isolated by paper electrophoresis and estimated by use of a specific enzymatic (choline kinase) - radioisotopic assay. The concentration of acetylcholine ranged from 25.5 to 1.1 nmol/g in the following tissues (in order of decreasing concentration): duodenum, corpus striatum, stomach, cerebral cortex, spinal cord, abdominal fat, submaxillary gland, kidney, adrenal gland, spleen, liver, lung, heart and diaphragm. Choline [methyl- 3-H] was converted in the tissues to acetylcholine within 3 minutes after intravenous administration of the precursor. Virtually all the radioactivity in plasma at that time was present as free choline, suggesting that free choline from plasma is the immediate precursor for acetylcholine synthesized in the tissues cited. The concentration of free choline in tissues ranged from 344 nmol/g in adrenals to 40 nmol/g in heart, while that in plasma was 15 nmol/g. The initial half-life of choline in plasma, estimated from the rate of disappearance of choline after intravenous administration of either a tracer dose of choline [methyl- 3-H] (0.031 mumol/kg) or a high dose of choline chloride (200 mumol/kg), was less than 1 minute. This rapid removal of choline from plasma resulted from uptake (or binding) by tissues, with kidney and liver removing about 50% of the administered dose of choline [methyl- 3-H] within 3 minutes after its administration. Uptake of choline occurred in all tissues cited above, but there was a 20-fold difference in the uptake by the most active tissues (kidney and adrenals), as compared to that of the least active (central nervous system). Within 60 minutes after administration of choline [methyl- 3-H], most of the radioactive choline taken up by tissues had been converted to organic-soluble metabolites and to water-soluble metabolites that behaved like either phosphorylcholine or betaine during paper electrophoresis and chromatography. Betaine was the principal metabolite of choline in plasma. Radioactivity was excreted slowly into urine, which contained primarily free choline, betaine and a large amount of an unidentified metabolite. These findings indicate that the principal mechanism for the rapid removal of choline from plasma is uptake into tissues followed by metabolism.
在戊巴比妥麻醉的豚鼠中研究了乙酰胆碱的生物合成以及静脉注射[甲基 - 3 - H]胆碱的代谢命运。通过纸电泳分离胆碱和乙酰胆碱，并使用特定的酶促（胆碱激酶） - 放射性同位素测定法进行估算。乙酰胆碱在以下组织中的浓度范围为25.5至1.1 nmol/g（浓度递减顺序）：十二指肠、纹状体、胃、大脑皮层、脊髓、腹部脂肪、颌下腺、肾脏、肾上腺、脾脏、肝脏、肺、心脏和膈肌。静脉注射前体后3分钟内，组织中的[甲基 - 3 - H]胆碱转化为乙酰胆碱。此时血浆中几乎所有的放射性都以游离胆碱形式存在，这表明血浆中的游离胆碱是上述组织中合成乙酰胆碱的直接前体。组织中游离胆碱的浓度范围从肾上腺中的344 nmol/g到心脏中的40 nmol/g，而血浆中的浓度为15 nmol/g。静脉注射示踪剂量的[甲基 - 3 - H]胆碱（0.031 μmol/kg）或高剂量的氯化胆碱（200 μmol/kg）后，根据胆碱消失速率估算的血浆中胆碱的初始半衰期小于1分钟。胆碱从血浆中的快速清除是由于组织摄取（或结合），肾脏和肝脏在注射[甲基 - 3 - H]胆碱后3分钟内清除了约50%的给药剂量。上述所有组织都摄取胆碱，但与活性最低的组织（中枢神经系统）相比，活性最高的组织（肾脏和肾上腺）的摄取量相差20倍。在注射[甲基 - 3 - H]胆碱后60分钟内，组织摄取的大部分放射性胆碱已转化为有机可溶性代谢物和水溶性代谢物，在纸电泳和色谱分析中其行为类似于磷酸胆碱或甜菜碱。甜菜碱是血浆中胆碱的主要代谢物。放射性缓慢排泄到尿液中，尿液中主要含有游离胆碱、甜菜碱和大量未鉴定的代谢物。这些发现表明，胆碱从血浆中快速清除的主要机制是被组织摄取然后进行代谢。
