Medical Faculty, Institute of Pharmacology and Toxicology, Martin-Luther-University Halle-Wittenberg, Magdeburger Str. 4, 06112, Halle (Saale), Germany.
Mol Cell Biochem. 2012 Jun;365(1-2):301-12. doi: 10.1007/s11010-012-1270-6. Epub 2012 Feb 25.
Pleiotropic effects of serotonin (5-HT) in the cardiovascular system are well documented. However, it remains to be elucidated, whether 5-HT is present in adult mammalian cardiomyocytes. To address this issue, we investigated the levels of 5-HT in blood, plasma, platelets, cardiac tissue, and cardiomyocytes from adult mice and for comparison in human right atrial tissue. Immunohistochemically, 5-HT was hardly found in mouse cardiac tissue, but small amounts could be detected in renal preparations, whereas adrenal preparations revealed a strong positive immunoreaction for 5-HT. Using a sensitive HPLC detection system, 5-HT was also detectable in the mouse heart and human atrium. Furthermore, we could identify 5-HT in isolated cardiomyocytes from adult mice. These findings were supported by detection of the activity of 5-HT-forming enzymes-tryptophan hydroxylase and aromatic L-amino acid decarboxylase-in isolated cardiomyocytes from adult mice and by inhibition of these enzymes with p-chlorophenylalanine and 3-hydroxybenzyl hydrazine. Addition of the first intermediate of 5-HT generation, that is 5-hydroxytryptophan, enhanced the 5-HT level and inhibition of monoamine oxidase by tranylcypromine further increased the level of 5-HT. Our findings reveal the presence and synthesis of 5-HT in cardiomyocytes of the mammalian heart implying that 5-HT may play an autocrine and/or paracrine role in the heart.
5-羟色胺(5-HT)在心血管系统中的多效作用已有充分的文献记载。然而,5-HT 是否存在于成年哺乳动物的心肌细胞中仍有待阐明。为了解决这个问题,我们检测了成年小鼠的血液、血浆、血小板、心脏组织和心肌细胞中的 5-HT 水平,并与人类右心房组织进行了比较。免疫组织化学分析显示,5-HT 在小鼠心脏组织中几乎检测不到,但在肾脏组织中可以检测到少量的 5-HT,而肾上腺组织则显示出强烈的 5-HT 阳性免疫反应。使用敏感的 HPLC 检测系统,也可以在小鼠心脏和人类心房中检测到 5-HT。此外,我们还可以从成年小鼠的分离的心肌细胞中鉴定出 5-HT。这些发现得到了以下证据的支持:在成年小鼠分离的心肌细胞中检测到 5-HT 形成酶-色氨酸羟化酶和芳香族 L-氨基酸脱羧酶的活性,并用对氯苯丙氨酸和 3-羟基苄肼抑制这些酶。添加 5-HT 生成的第一个中间产物,即 5-羟色氨酸,可以提高 5-HT 的水平,而用曲马多抑制单胺氧化酶进一步增加 5-HT 的水平。我们的发现揭示了哺乳动物心脏的心肌细胞中存在 5-HT 的合成,这表明 5-HT 可能在心脏中发挥自分泌和/或旁分泌作用。