Young Lindsey W, Darios Emma S, Watts Stephanie W
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Histochem Cell Biol. 2015 Oct;144(4):321-9. doi: 10.1007/s00418-015-1343-1. Epub 2015 Jul 31.
5-Hydroxytryptamine (5-HT) was originally discovered as a vasoconstrictor. 5-HT lowers blood pressure when administered peripherally to both normotensive and hypertensive male rats. Because the serotonin transporter (SERT) can function bidirectionally, we must consider whether 5-HT can be transported from the bloodstream to the central nervous system (CNS) in facilitating the fall in blood pressure. The blood-brain barrier (BBB) is a highly selective barrier that restricts movement of substances from the bloodstream to the CNS and vice versa, but the rat BBB has not been investigated in terms of SERT expression. This requires us to determine whether the BBB of the rat, the species in which we first observed a fall in blood pressure to infused 5-HT, expresses SERT. We hypothesized that SERT is present in the BBB of the male rat. To test this hypothesis, over 500 blood vessels were sampled from coronal slices of six male rat brains. Immunofluorescence of these coronal slices was used to determine whether SERT and RecA-1 (an endothelial cell marker) colocalized to the BBB. Blood vessels were considered to be capillaries if they were between 1.5 and 23 µm (intraluminal diameter). SERT was identified in the largest pial vessels of the BBB (mean ± SEM = 228.70 ± 18.71 µm, N = 9) and the smallest capillaries (mean ± SEM = 2.75 ± 0.12 µm, N = 369). SERT was not identified in the endothelium of blood vessels ranging from 20 to 135 µm (N = 45). The expression of SERT in the rat BBB means that 5-HT entry into the CNS must be considered a potential mechanism when investigating 5-HT-induced fall in blood pressure.
5-羟色胺(5-HT)最初被发现是一种血管收缩剂。当对正常血压和高血压雄性大鼠进行外周给药时,5-HT会降低血压。由于血清素转运体(SERT)具有双向功能,因此我们必须考虑在促进血压下降过程中,5-HT是否能从血液转运至中枢神经系统(CNS)。血脑屏障(BBB)是一种高度选择性的屏障,它限制物质在血液和中枢神经系统之间的移动,反之亦然,但尚未对大鼠血脑屏障的SERT表达进行研究。这就要求我们确定在我们首次观察到注入5-HT后血压下降的大鼠物种中,其血脑屏障是否表达SERT。我们假设雄性大鼠的血脑屏障中存在SERT。为了验证这一假设,从六只雄性大鼠大脑的冠状切片中采集了500多条血管样本。利用这些冠状切片的免疫荧光来确定SERT和RecA-1(一种内皮细胞标记物)是否共定位于血脑屏障。如果血管的管腔内直径在1.5至23微米之间,则被视为毛细血管。在血脑屏障最大的软脑膜血管(平均值±标准误=228.70±18.71微米,N=9)和最小的毛细血管(平均值±标准误=2.75±0.12微米,N=369)中鉴定出了SERT。在直径为20至135微米的血管内皮中未鉴定出SERT(N=45)。大鼠血脑屏障中SERT的表达意味着在研究5-HT诱导的血压下降时,必须考虑5-HT进入中枢神经系统这一潜在机制。