Transepithelial Transport Characteristics of the Antihypertensive Peptide, Lys-Val-Leu-Pro-Val-Pro, in Human Intestinal Caco-2 Cell Monolayers

Abstract

An antihypertensive peptide, Lys-Val-Leu-Pro-Val-Pro (KVLPVP), can reduce blood pressure in hypertensive rats after being orally administered. In this study, the transepithelial transport of intact KVLPVP was examined by Caco-2 monolayers. The results were as follows: (i) The flux was not saturable for apical (AP) to basolateral (BL) or BL-AP transport when the concentration of KVLPVP was 1-8 mM. (ii) Sodium deoxycholate loosened the tight junction in the Caco-2 cells and significantly improved the transport process. (iii) Phenylarsine oxide, a transcytotic process inhibitor, had little effect on the transport process. (iv) The influx and eflux of KVLPVP remained unchanged in the presence of the ATP inhibitor sodium azide. (v) This transport was not inhibited by the peptide transporter substrates Gly-Pro or arphanine A. All these data indicate that paracellular transport diffusion was the major flux mechanism for the intact KVLPVP.

Transport of ACE Inhibitory Peptides Ile‐Gln‐Pro and Val‐Glu‐Pro Derived from Spirulina platensis Across Caco‐2 Monolayers

“…When IQP and VEP were added at 1 mM to the AP side, the peptides were detected as 13.58 and 20.12 μM, respectively at BL side. These were higher than that of QIGLF (Ding et al., ) and KVLPVP (Sun, Liu, Li, & Qin, ), both of which had been identified with significant ACE inhibitory activities. Same concentration was used in the studies of two peptides in order to control variables.…”

“…Detected concentration in BL side indicated that approximately 3% of peptide was transported. This was higher than KVLPVL (Sun et al., ), Gly‐Ala‐Hyp‐Gly‐Leu‐Hyp‐Gly‐Pro (Shimizu et al., ) and many other peptides which had all been identified with significant ACE inhibitory activities. The specific construction of the peptide, such as hydrophobic uncharged residues, was probably one of the reasons that led to the high permeability (Ding et al., ).…”

Current understanding of transport and bioavailability of bioactive peptides derived from dairy proteins: a review

“…The human GIT has many paracellular diffusion pores, also called TJs consisting of zonula occludens‐1, occludin and claudin proteins. Table shows that a variety of DBPs are transported by the energy‐independent paracellular route via TJs (Quirós et al ., ), such as His‐Leu‐Pro‐Leu‐Pro (HLPLP; Quirós et al ., ), Lys‐Val‐Leu‐Pro‐Val‐Pro (KVLPVP; Sun et al ., ), LKP (Gleeson et al ., , ; Xu et al ., ), Arg‐Leu‐Ser‐Phe‐Asn‐Pro (RLSFNP; Guo et al ., ), Arg‐Trp‐Gln (RWQ), Trp‐Gln (WQ; Fernández‐Musoles et al ., ), Ser‐Arg‐Tyr‐Pro‐Ser‐Tyr (SRYPSY), Tyr‐Pro‐Phe‐Pro‐Gly (YPFPG), Tyr‐Pro‐Phe‐Pro‐Gly‐Pro‐Ile (YPFPGPI; Sienkiewicz‐Szłapka et al ., ), Val‐Leu‐Pro‐Val‐Pro (VLPVP; Lei et al ., ) and VPP (Satake et al ., ). However, β‐casein‐f(193–209) cannot be transported via diffusion due to its long length and hydrophobicity (Regazzo et al ., ).…”

Bioactive Peptides from Muscle Sources: Meat and Fish

“…Peptides may be hydrolyzed by enzymes of the digestive tract as well as peptidases associated with the brush border membrane, cytoplasm or serum [59,60]. To date, studies documenting the intestinal absorption of ACE inhibitory peptides in vitro have employed the Caco-2 cell monolayer [61], as it is generally acknowledged that this cell line is a suitable model to predict the permeability of intestinal epithelial cells to pharmaceuticals [62,63,64].…”