Implication of Opioid Receptors in the Antihypertensive Effect of a Novel Chicken Foot-Derived Peptide.

Anna Mas-Capdevila,Gerard Aragonès,Lisard Iglesias-Carres,Francisca Isabel Bravo,Begoña Muguerza,Anna Arola-Arnal

doi:10.3390/biom10070992

Abstract

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.

Highlights

Bioactive peptides are specific protein fragments released by limited proteolysis of their specific precursor proteins, which present additional biological activities over and above their expected nutritional [1,2]
Food proteins contain specific peptide sequences that are inactive as long as they remain bonded to other amino acids within the primary protein structure, which might be released by protein hydrolysis [27]
It has been demonstrated that the hydrolysis of chicken foot proteins is a good strategy for the obtaining of bioactive peptides able to reduce blood pressure (BP) [22,24]

Summary

Introduction

Bioactive peptides are specific protein fragments released by limited proteolysis of their specific precursor proteins, which present additional biological activities over and above their expected nutritional [1,2]. One of the most important biological properties attributed to bioactive peptides is their antihypertensive effects [4]. These peptides are usually obtained and selected by their capacity to inhibit angiotensin-converting enzyme (ACE), key enzyme in blood pressure (BP) regulation [5]. Hypertension (HTN) is a global public health problem [6] and its medical treatment is well established, it can present side-effects in some patients [7]. The use of antihypertensive peptides as an alternative for HTN prevention and treatment is receiving interest even though these inhibitory peptides present lower ACE inhibitory (ACEI) activity than the antihypertensive drugs [4]

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Methods

Results