Araneda S, Mermet A, Buda M, Bobillier P, Pujol J F
INSERM U 171, Laboratoire de Médecine Expérimentalle, Université Claude Bernard, 8, avenue Rockefeller, 6973 Lyon Cedex 2, France.
Neurochem Int. 1984;6(1):27-39. doi: 10.1016/0197-0186(84)90023-8.
A biochemical analysis of radioactive compounds was performed in the olfactory bulb (OB) and raphe dorsalis (RD) after injection of radioactive [(3)H] or [(14)C]serotonin (5-HT ranging from 10(?2) M to 10(?7) M) into the OB of rats treated or not with a monoamine-oxidase inhibitor (MAOI). In the OB of untreated rats, radioactivity was associated with precipitated protein and soluble perchloric acid (PCA) fractions. High performance liquid chromatography (HPLC) analysis of the PCA-supernatant gave 4 radioactive peaks: one associated with endogenous 5-HT, another with endogenous 5-hydroxyindole acetic acid (5-HIAA) and two without any relationship with endogenous hydroxyindoles: a '5-HT derivative A' and a '5-HT derivative B'. The presence of these '5-HT derivatives' was significantly reduced after treatment with 5,6-dihydroxytryptamine. In the RD, radioactivity was associated with the protein fraction and with '5-HT derivative A'. The kinetic analysis (from 30 min to 46 h) of the '5-HT derivative A' was characterized by a disappearance in the OB and an accumulation in the RD corresponding to a rate of migration in a range of 0.7 to 2 mm/h. This compound was absent or negligible in other non-serotoninergic neurons (such as the Locus Coeruleus, Amygdala and Cortex piriformis). No clear evidence for retrograde transport of radioactive 5-hydroxytryptophan (5-HTP) or 5-HIAA was found. At lower concentration of 5-HT injected into the OB, the half lives and the times of maximal accumulation for 5-HIAA, '5-HT derivative A' and '5-HT derivative B' were increased. The specific activity of 5-HT and 5-HIAA was also increased. The selective radioactive accumulation in the cell bodies of RD neurons after injection of radioactive 5-HT into the OB is discussed as resulting from a selectivity in (a) the uptake by 5-HT nerve terminals; (b) the metabolism of 5-HT into '5-HT derivative A' in the OB; (c) the retrograde axonal transport of '5-HT derivative A'. This '5-HT derivative A' could represent a messenger between nerve terminals and cell bodies and could be involved in homeostatic mechanisms that maintain cellular dynamics. When a MAOI was used, '5-HT-derivative A' and [(3)H]5-HT were found in the OB and also in the RD cell bodies, and to a lesser extent, in the non-serotoninergic cell bodies. These results indicate that MAO inhibition produces a relative non-selectivity in the 'uptake-metabolism and retrograde axonal transport' systems.
在给或不给单胺氧化酶抑制剂（MAOI）处理的大鼠嗅球（OB）注射放射性[(3)H]或[(14)C]血清素（5 - HT，浓度范围为10⁻²M至10⁻⁷M）后，对嗅球和中缝背核（RD）中的放射性化合物进行了生化分析。在未处理大鼠的嗅球中，放射性与沉淀蛋白和可溶性高氯酸（PCA）组分相关。对PCA上清液的高效液相色谱（HPLC）分析给出了4个放射性峰：一个与内源性5 - HT相关，另一个与内源性5 - 羟吲哚乙酸（5 - HIAA）相关，还有两个与内源性羟吲哚无关：一个“5 - HT衍生物A”和一个“5 - HT衍生物B”。用5,6 - 二羟基色胺处理后，这些“5 - HT衍生物”的存在显著减少。在中缝背核中，放射性与蛋白组分以及“5 - HT衍生物A”相关。“5 - HT衍生物A”的动力学分析（从30分钟到46小时）的特征是在嗅球中消失而在中缝背核中积累，对应迁移速率在0.7至2毫米/小时范围内。该化合物在其他非5 - 羟色胺能神经元（如蓝斑、杏仁核和梨状皮质）中不存在或可忽略不计。未发现放射性5 - 羟色氨酸（5 - HTP）或5 - HIAA逆行运输的明确证据。向嗅球注射较低浓度的5 - HT时，5 - HIAA、“5 - HT衍生物A”和“5 - HT衍生物B”的半衰期和最大积累时间增加。5 - HT和5 - HIAA的比活性也增加。将放射性5 - HT注入嗅球后，中缝背核神经元细胞体中的选择性放射性积累被认为是由于（a）5 - HT神经末梢摄取的选择性；（b）嗅球中5 - HT代谢为“5 - HT衍生物A”的选择性；（c）“5 - HT衍生物A”的逆行轴突运输的选择性。这种“5 - HT衍生物A”可能代表神经末梢与细胞体之间的信使，并可能参与维持细胞动态的稳态机制。当使用MAOI时，在嗅球以及中缝背核细胞体中发现了“5 - HT衍生物A”和[(3)H]5 - HT，在较小程度上，在非5 - 羟色胺能细胞体中也有发现。这些结果表明MAO抑制在“摄取 - 代谢和逆行轴突运输”系统中产生了相对的非选择性。
