Mück-Seler D, Diksic M
Laboratory for Molecular Neuropharmacology, Ruder Bosković Institute, Zagreb, Croatia.
Neuropsychopharmacology. 1995 May;12(3):251-62. doi: 10.1016/0893-133X(94)00084-D.
The rate of serotonin (5-HT) synthesis was measured in the discrete regions of the rat brain utilizing an autoradiographic method and alpha[14C]methyl-L-tryptophan as a tracer after an acute treatment with reserpine (10 mg/kg IP) or NSD-1015 (m-hydroxybenzylhydrazine) (100 mg/kg IP). Controls were injected with the same volume of solvent in place of reserpine or NSD-1015. Our results showed that reserpine induced a statistically significant (except for medial geniculate body) decrease in the rate of 5-HT synthesis in a large number of discrete brain structures. Reserpine had no influence on the plasma concentration of amino acids sharing the same carrier with tryptophan nor on the fraction of plasma-free tryptophan. NSD-1015 induced a statistically significant increase (p < .05) in the rate of 5-HT synthesis in 20 out of 28 brain regions but produced a pronounced decrease in the rate of 5-HT synthesis in the pineal body. This decrease in the pineal body serotonin synthesis rate is most likely the result of the loss of the label in the form of 5-hydroxy-alpha[14C]methyl-L-tryptophan [5-OHMTrp] that is not metabolized further because aromatic amino acid decarboxylase was inhibited. The data showing that there was no loss of the 5-OHMTrp from other brain structures as result of reserpine are also given. NSD-1015 treatment also induced a time-dependent increase in the plasma concentration of free tryptophan that becomes significant 30 minutes after NSD-1015 injection. Our results suggest that reserpine induces a decrease in 5-HT synthesis probably via direct or indirect inhibition of tryptophan hydroxylase activity. Since NSD-1015 alone increased the rate of 5-HT synthesis, the measurement of 5-HT synthesis in previous experiments using NSD-1015 and measuring the rate of 5-hydroxytryptophan accumulation after NSD-1015 induced inhibition of decarboxylase activity should be interpreted with reservation.
利用放射自显影法，以α[¹⁴C]甲基-L-色氨酸作为示踪剂，在利血平（10mg/kg腹腔注射）或NSD-1015（间羟基苄基肼）（100mg/kg腹腔注射）急性处理后，测定大鼠脑离散区域中5-羟色胺（5-HT）的合成速率。对照组注射相同体积的溶剂以替代利血平或NSD-1015。我们的结果显示，利血平使大量离散脑结构中5-HT的合成速率出现统计学显著下降（内侧膝状体除外）。利血平对与色氨酸共用同一载体的血浆氨基酸浓度以及血浆游离色氨酸的比例均无影响。NSD-1015使28个脑区中的20个脑区5-HT的合成速率出现统计学显著升高（p < 0.05），但使松果体中5-HT的合成速率显著降低。松果体中5-HT合成速率的这种降低很可能是由于5-羟基-α[¹⁴C]甲基-L-色氨酸[5-OHMTrp]形式的标记物丢失所致，因为芳香族氨基酸脱羧酶受到抑制，该标记物无法进一步代谢。文中还给出了数据，表明利血平处理后其他脑结构中未出现5-OHMTrp的丢失。NSD-1015处理还导致血浆游离色氨酸浓度随时间增加，在注射NSD-1015后30分钟变得显著。我们的结果表明，利血平可能通过直接或间接抑制色氨酸羟化酶活性来降低5-HT的合成。由于单独使用NSD-1015会增加5-HT的合成速率，因此在先前使用NSD-1015并在NSD-1015诱导脱羧酶活性抑制后测量5-羟色氨酸积累速率来测定5-HT合成的实验结果应谨慎解读。
