Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Eur J Med Res. 2010 Nov 4;15 Suppl 2(Suppl 2):128-34. doi: 10.1186/2047-783x-15-s2-128.
Serotonin (5-HT) and its receptors are present in central, the brain stem, and peripheral, the carotid body, tissues controlling the ventilatory responses to hypoxia. The exact action of serotonin and its nature are, however, unsettled. We hypothesized that the discrepant results on the ventilatory action of serotonin could be caused by the inability of serotonin to penetrate into the brain or the plasma membrane lipid bilayers, the target site of signal transduction cascades, after its exogenous administration.
To study the penetrability of novel lipid derivatives of serotonin of varying fatty acid chain length and number of saturated/unsaturated bonds, the oleic, caprylic, and caprolic amides of 5-HT, into the brain, and their functional effects on the hypoxic ventilatory response in awake rats after systemic administration.
Adult Wistar rats were used for the experiments. In the biochemical part of the study, the presence and stability of the compounds tested, after i.p. injection, was assessed in brain extracts using spectrophotometry and thin-layered chromatography. In the functional part, the ventilatory responses to 8 and 12% hypoxia were compared before and 1 h after the compound administration using a whole body plethysmography.
The "lipidized" serotonin compounds turned out to be stable in brain extracts in vitro for up to 3 h of the test. However, we could not substantiate the presence of any of the compounds in the brain, with either method used, after i.p. administration. Likewise, none of the compounds had any appreciable effect on the profile of the stimulatory hypoxic ventilatory response.
Synthetically attaching lipophilic groups to the serotonin molecule does not make it penetrate into the brain. The lack of serotonin penetrability likely depends on the planarity of its molecule, as it does not seem to depend on the size, number of carbons or bond saturation of the "lipidized" molecules. Such molecules do not directly interfere with the carotid chemoreceptor-mediated hypoxic ventilatory response. The study failed to substantiate the bioactive potential of the lipid derivatives of serotonin.
血清素（5-HT）及其受体存在于中枢神经系统、脑干和外周组织，即颈动脉体，这些组织控制着对缺氧的通气反应。然而，血清素的确切作用及其性质尚未确定。我们假设，由于外源性给予血清素后，其不能穿透血脑屏障或质膜双层，即信号转导级联的靶位，因此，血清素对通气作用的不一致结果可能是由其引起的。
研究不同脂肪酸链长和饱和/不饱和键数的新型血清素脂质衍生物，即 5-HT 的油酸酰胺、辛酸酰胺和己酸酰胺，进入大脑的穿透能力，以及它们在全身给药后对清醒大鼠缺氧性通气反应的功能影响。
本研究采用成年 Wistar 大鼠进行实验。在研究的生化部分，使用分光光度法和薄层色谱法评估腹腔注射后测试化合物在脑提取物中的存在和稳定性。在功能部分，使用全身 plethysmography 在化合物给药前和给药后 1 小时比较 8%和 12%缺氧时的通气反应。
“脂质化”的血清素化合物在体外脑提取物中稳定，测试时间长达 3 小时。然而，我们无法使用任何一种方法，在腹腔给药后，在脑内证实任何一种化合物的存在。同样，没有一种化合物对刺激性缺氧性通气反应的特征有明显影响。
将亲脂基团合成连接到血清素分子上并不会使其穿透血脑屏障。血清素穿透能力的缺乏可能取决于其分子的平面性，因为它似乎不取决于“脂质化”分子的大小、碳原子数量或键饱和度。这些分子不会直接干扰颈动脉体化学感受器介导的缺氧性通气反应。该研究未能证实血清素脂质衍生物的生物活性潜力。
