Serotonin, a downstream effector of GLP-2, enhances lacteal contractility and lymph flow.

IF 3.3 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Lili Tian, Majid Mufaqam Syed-Abdul, Gary F Lewis
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引用次数: 0

Abstract

Glucagon-like peptide-2 (GLP-2) is known to exert some of its biological effects via the release of neurotransmitters, and in view of the absolute requirement for the enteric nervous system (ENS) demonstrated in our recent GLP-2-induced lipid mobilization studies, we aimed to identify the neurotransmitter that mediates GLP-2's effect on intestinal lipid mobilization. We also examined the role of VEGFR3 as an intermediate in the signaling cascade. Utilizing a rat lymph fistula model, 5 hours after an intraduodenal (i.d.) lipid bolus, the following intraperitoneal (i.p.) administrations were applied in two different sets of experiments: Experiment 1: 1) Placebo, 2) GLP-2, 3) GLP-2 + Ketanserin (serotonin receptor antagonist). Experiment 2: 1) Placebo, 2) Serotonin, 3) Serotonin + MAZ-51 (a VEGFR3 inhibitor), 4) Serotonin + SAR131675 (a second VEGFR3 inhibitor). Lymph flow and triglyceride (TG) output were assessed for 60 mins (Experiment 1) or 90 mins (Experiment 2) after administration. In another set of animals, GLP-2 or serotonin were administered i.p and blood samples were collected to quantify plasma serotonin concentration. Intravital imaging of a prospero-related homeobox 1-enhanced green fluorescent protein rat model was utilized to assess lacteal contractility after placebo or serotonin administration. We demonstrated that single-dose GLP-2 administration acutely increased serotonin concentration in plasma, serotonin enhanced lymph flow, lymph TG output and lacteal contractility, antagonism of the serotonin receptor decreases GLP-2-enhanced mesenteric lymph flow and TG output and inhibition of VEGFR3 abolished serotonin-induced lymph flow and TG output.

血清素,GLP-2的下游效应,增强乳收缩性和淋巴流动。
已知胰高血糖素样肽-2 (GLP-2)通过释放神经递质来发挥其一些生物学作用,鉴于我们最近在GLP-2诱导的脂质动员研究中证明了对肠神经系统(ENS)的绝对需求,我们旨在确定介导GLP-2对肠道脂质动员作用的神经递质。我们还研究了VEGFR3作为信号级联中的中间体的作用。利用大鼠淋巴瘘模型,在十二指肠内(i.d)脂质丸5小时后,在两组不同的实验中应用以下腹腔内(i.p)给药:实验1:1)安慰剂,2)GLP-2, 3) GLP-2 +酮色林(5 -羟色胺受体拮抗剂)。实验2:1)安慰剂,2)血清素,3)血清素+ MAZ-51(一种VEGFR3抑制剂),4)血清素+ SAR131675(另一种VEGFR3抑制剂)。在给药后60分钟(实验1)或90分钟(实验2)评估淋巴流量和甘油三酯(TG)输出。在另一组动物中,腹腔注射GLP-2或5 -羟色胺,并收集血液样本以定量血浆5 -羟色胺浓度。使用与繁荣相关的homeobox 1增强绿色荧光蛋白大鼠模型的活体成像来评估安慰剂或5 -羟色胺给药后的乳收缩性。我们证明,单剂量GLP-2急性增加血浆中5 -羟色胺浓度,5 -羟色胺增强淋巴流量、淋巴TG输出和乳收缩性,5 -羟色胺受体拮抗降低GLP-2增强的肠系膜淋巴流量和TG输出,抑制VEGFR3可消除5 -羟色胺诱导的淋巴流量和TG输出。
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来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
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