Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili, 43007 Tarragona, Spain.
EURECAT-Technology Centre of Catalonia, Technological Unit of Nutrition and Health, 43204 Reus, Spain.
Biomolecules. 2020 Jul 2;10(7):992. doi: 10.3390/biom10070992.
The peptide AVFQHNCQE demonstrated to produce nitric oxide-mediated antihypertensive effect. This study investigates the bioavailability and the opioid-like activity of this peptide after its oral administration. For this purpose, in silico and in vitro approaches were used to study the peptide susceptibility to GI digestion. In addition, AVFQHNCQE absorption was studied both in vitro by using Caco-2 cell monolayers and in vivo evaluating peptide presence in plasma from Wistar rats by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and by ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Both in vivo and in vitro experiments demonstrated that peptide AVFQHNCQE was not absorbed. Thus, the potential involvement of opioid receptors in the BP-lowering effect of AVFQHNCQE was studied in the presence of opioid receptors-antagonist Naloxone. No changes in blood pressure were recorded in rats administered Naloxone, demonstrating that AVFQHNCQE antihypertensive effect is mediated through its interaction with opioid receptors. AVFQHNCQE opioid-like activity would clarify the antihypertensive properties of AVFQHNCQE despite its lack of absorption.
该肽 AVFQHNCQE 被证明具有产生一氧化氮介导的降压作用。本研究调查了该肽口服后的生物利用度和类阿片样活性。为此，使用计算和体外方法研究了肽对胃肠道消化的敏感性。此外，通过使用 Caco-2 细胞单层在体外研究了 AVFQHNCQE 的吸收，并通过超高效液相色谱-串联质谱 (UHPLC-MS/MS) 和超高效液相色谱-高分辨质谱 (UHPLC-HRMS) 在体内评估 Wistar 大鼠血浆中肽的存在来评估其吸收情况。体内和体外实验均表明肽 AVFQHNCQE 未被吸收。因此，在存在阿片受体拮抗剂纳洛酮的情况下，研究了 AVFQHNCQE 降低血压作用与阿片受体的潜在关系。给予纳洛酮的大鼠血压没有变化，这表明 AVFQHNCQE 的降压作用是通过其与阿片受体的相互作用介导的。AVFQHNCQE 的类阿片样活性将阐明 AVFQHNCQE 的降压特性，尽管其吸收不足。
