FORMATION OF A BETA-CARBOLINE (1,2,3,4-TETRAHYDRO-1-METHYL-BETA-CARBOLINE-1-CARBOXYLIC ACID) FOLLOWING INTRACEREBROVENTRICULAR INJECTION OF TRYPTAMINE AND PYRUVIC-ACID
FORMATION OF A BETA-CARBOLINE (1,2,3,4-TETRAHYDRO-1-METHYL-BETA-CARBOLINE-1-CARBOXYLIC ACID) FOLLOWING INTRACEREBROVENTRICULAR INJECTION OF TRYPTAMINE AND PYRUVIC-ACID
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DOI：
10.1007/bf00165039
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发表时间：
1987-01-01
影响因子：
3.6
通讯作者：
ROMMELSPACHER, H
中科院分区：
文献类型：
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作者：
SUSILO, R;ROMMELSPACHER, H
氚标记的1-羧基-四氢哈曼在大鼠脑中被鉴定为i. c. v.注射[3 H]色胺和维生素C。在i.c.v注射前30分钟，用MAO抑制剂帕吉林（40 mg/kg）处理动物。在这些条件下，在脑中只能检测到痕量的[3 H]吲哚乙酸。1-CTHH的形成具有时间依赖性。i. c. v.注射后5分钟，约0.45%的给药色胺转化为1-CTHH，23%仍保持不变。放射性1-CTHH的量在1小时内略有增加（0.8%; [3 H]色胺：6%）。用高剂量帕吉林（75 mg/kg; i. c. v.注射前90 min）预处理大鼠可防止[3 H]1-CTHH和[3 H]吲哚乙酸（IAA）的形成，表明高剂量帕吉林抑制1-CTHH的形成。作为1-CTHH可能的非酶促形成的对照，将[3 H]色胺和各种浓度的异甘草酸在pH 7.4的磷酸盐缓冲液中孵育。1-在这些条件下未检测到CTHH。然而，在高浓度（终浓度= 100 mM）和低pH值（<pH 4）下观察到1-CTHH的形成。为了支持观察到的两种前体在细胞内发生1-CTHH缩合的假设，研究了色胺的代谢。i. c. v.注射[3 H]色胺后2分钟，约4%的注射剂量保持不变，10%代谢为[3 H]IAA。这些发现表明[3 H]色胺从脑脊液中迅速消失，并迅速渗透到脑组织中。通过在各种溶剂系统中的薄层色谱法，甲基化产生的甲酯衍生物，并在体外脱羧为哈马兰与大鼠肝匀浆和PLP作为辅酶后，在体内给药的前体后形成的1-CTHH进行鉴定。本发明的结果提示了β-半乳糖苷生物合成的替代途径。大鼠中的咔啉。
Tritium labelled 1-carboxy-tetrahydroharman was identified in rat brain following i.c.v.-injection of [3H]tryptamine and pyruvic acid. The animals had been treated with the MAO inhibitor pargyline (40 mg/kg) 30 min before i.c.v injection. Under these conditions, only trace amounts of [3H]indole acetic acid could be detected in the brain. The formation of 1-CTHH was time-dependent. Five minutes following the i.c.v. injection, approximately 0.45% of the administered tryptamine was converted into 1-CTHH and 23% were still unchanged. The amount of the radioactive 1-CTHH increased slightly within 1 h (0.8%; [3H]tryptamine: 6%). Pretreatment of the rats with high doses of pargyline (75 mg/kg; 90 min before i.c.v. injection) prevented the formation of both [3H]1-CTHH and [3H]indole acetic acid (IAA) suggesting that high doses of pargyline inhibit the formation of 1-CTHH. As control for a possible non-enzymatic formation of 1-CTHH, [3H]tryptamine and various concentrations of pyruvic acid were incubated in phosphate buffer at pH 7.4. 1-CTHH was not detected under these conditions. However, the formation of 1-CTHH was observed at high pyruvic acid concentrations (final concentration = 100 mM) and low pH values [< pH4). To support the assumption that the observed condensation of both precursors to 1-CTHH occurred intracellularly, the metabolism of tryptamine was studied. Two minutes after i.c.v. injection of [3H]tryptamine approximately 4% of the injected dose remained unchanged and 10% were metabolized to [3H]IAA. These findings suggest a rapid disappearance of [3H]tryptamine from the cerebrospinal fluid as well as a rapid penetration into the cerebral tissue. The identification of the 1-CTHH formed after in vivo administration of both precursors was carried out by thin layer chromatography in various solvent systems, methylation yielding the methyl ester derivative and in vitro decarboxylation to harmalan with rat liver homogenate and PLP as co-enzyme. The present results suggest an alternative pathway for the biosynthesis of .beta.-carbolines in rats.