Li Q, Murakami I, Stall S, Levy A D, Brownfield M S, Nichols D E, Van de Kar L D
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA.
J Pharmacol Exp Ther. 1996 Dec;279(3):1261-7.
Serotonin (5-hydroxytryptamine, 5-HT)-releasing drugs are important experimental tools to examine the role of serotonergic nerve terminals in the secretion of hormones. The drugs 1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (MBDB), 5-methoxy-6-methyl-2-aminoindan (MMAI) and p-methylthioamphetamine (MTA) have been suggested to be 5-HT releasers. The present study characterized MBDB, MMAI and MTA by using their effects on the secretion of the hormones adrenal corticotrophin (ACTH), corticosterone, prolactin, oxytocin and renin. The time course of the effect of MBDB, MMAI and MTA (5 mg/kg, i.p.) showed that the peak effect on plasma ACTH occurred 10 min after the injection, whereas the prolactin response did not reach a maximum until 30 min after injection. MBDB increased plasma renin concentration within 10 min, whereas the effect of MTA was significant only at 30 min after injection. All three 5-HT releasers decreased HR (within 5 min) and blood pressure (at 15 min after injection). MBDB, MMAI and MTA increased plasma ACTH, corticosterone, prolactin and renin levels in a dose-dependent manner, whereas no changes were observed in plasma vasopressin concentrations. MTA and MMAI, but not MBDB, significantly increased plasma oxytocin concentrations in a dose-dependent manner. Pretreatment of rats with fluoxetine blocked the ACTH response to MBDB and MMAI, but not to MTA. The prolactin response to all three 5-HT releasers was blocked by fluoxetine. The oxytocin response to MTA and MMAI was inhibited by fluoxetine. The renin responses to all three 5-HT releasers were not significantly inhibited by fluoxetine. The results suggest that MBDB, MMAI and MTA can increase the secretion of several hormones, at least in part, through stimulation of serotonergic neurotransmission. However, these three 5-HT releasers seem to have effects on other (and as yet uncharacterized) mechanisms that can stimulate the secretion of some hormones.
5-羟色胺（5-羟色胺，5-HT）释放药物是研究5-羟色胺能神经末梢在激素分泌中作用的重要实验工具。1-(1,3-苯并二氧杂环戊烯-5-基)-2-(甲氨基)丁烷（MBDB）、5-甲氧基-6-甲基-2-氨基茚满（MMAI）和对甲基硫代苯丙胺（MTA）被认为是5-HT释放剂。本研究通过观察MBDB、MMAI和MTA对肾上腺皮质激素（ACTH）、皮质酮、催乳素、催产素和肾素分泌的影响来对其进行特性描述。MBDB、MMAI和MTA（5mg/kg，腹腔注射）作用的时间进程表明，对血浆ACTH的峰值效应在注射后10分钟出现，而催乳素反应直到注射后30分钟才达到最大值。MBDB在10分钟内增加血浆肾素浓度，而MTA的作用仅在注射后30分钟时显著。所有三种5-HT释放剂均降低心率（在5分钟内）和血压（在注射后15分钟时）。MBDB、MMAI和MTA以剂量依赖性方式增加血浆ACTH、皮质酮、催乳素和肾素水平，而血浆血管加压素浓度未观察到变化。MTA和MMAI，但不是MBDB，以剂量依赖性方式显著增加血浆催产素浓度。用氟西汀预处理大鼠可阻断对MBDB和MMAI的ACTH反应，但不阻断对MTA的反应。对所有三种5-HT释放剂的催乳素反应均被氟西汀阻断。对MTA和MMAI的催产素反应被氟西汀抑制。对所有三种5-HT释放剂的肾素反应未被氟西汀显著抑制。结果表明，MBDB、MMAI和MTA至少部分地通过刺激5-羟色胺能神经传递来增加几种激素的分泌。然而，这三种5-HT释放剂似乎对其他（尚未明确的）能够刺激某些激素分泌的机制有影响。
