Transport of Val-Leu-Pro-Val-Pro in Human Intestinal Epithelial (Caco-2) Cell Monolayers

Abstract

Angiotensin converting enzyme (ACE) inhibitory peptides are biologically active peptides that play a very important role in blood pressure regulation. In previous experiments, we obtained an ACE inhibitory peptide Val-Leu-Pro-Val-Pro (VLPVP) by DNA recombinant technology. The purpose of this study was to examine the bidirectional transport of VLPVP by using the human intestinal Caco-2 monolayers. The permeability coefficient ( P app) values of VLPVP over 4-8 mmol/L ranged from 7.44 x 10(-8) to 1.35 x 10(-6) cm/s for apical (AP) to basolateral (BL) transport, while the P app values for BL to AP flux were significantly lower than those for the AP to BL flux, with efflux ratio values of 0.74-0.13 over 4-8 mM. Preincubation of the paracellular transport enhancer (sodium deoxycholate), the inhibitor of multidrug resistant protein (MK-571), or sodium azide stimulated efflux of VLPVP significantly ( p < 0.01); these results indicate that the transport of VLPVP across Caco-2 monolayers was involved in paracellular diffusion and MRP2 transport.

Visualized absorption of anti‐atherosclerotic dipeptide, Trp‐His, in Sprague–Dawley rats by LC‐MS and MALDI‐MS imaging analyses

“…It was clear that both dipeptides were able to be transported across Caco‐2 cell monolayers with >fivefold lower transportability than Gly‐Sar. However, their P app values of 4.6–8.1 × 10 −6 cm/s were much higher than those reported for Caco‐2 cell transportable oligopeptides through TJ pathway such as Val‐Pro‐Pro (0.21 × 10 −6 cm/s) and Val‐Leu‐Pro‐Val‐Pro (1.35 × 10 −6 cm/s) . A significantly ( p < 0.05) higher P app value of Trp‐His than that of His‐Trp was in good agreement with that reported by Ano et al.…”

The (193–209) 17‐residues peptide of bovine β‐casein is transported through Caco‐2 monolayer

“…To study the resistance of the b-CN (193-209) peptide to brush-border membrane peptidases, we used Caco-2 cell monolayer because, under specific culture conditions, Caco-2 cells undergo a process of differentiation leading to the expression of several morphological and functional characteristics of the enterocyte including the microvillus structure and of brush-border enzymes in the apical membrane [30,31] action of intracellular peptidases. In general, due to their rapid hydrolysis by the brush border or cytoplasmic peptidases, the bioavailability of two to nine residues-peptides is extremely low [13,21,23,24,26,28,29,32]. The resistance of the b-CN (193-209) peptide to the action of Caco-2 brushborder peptidases is possibly related to its proline-rich sequence (four proline residues on 17 residues), and other proline-containing peptides were found to be resistant to intestinal proteolysis [33,34].…”

Polystyrene nanoparticle trafficking across MDCK-II

“…To determine effects of metabolic inhibition/energy depletion, flux across MDCK-II was measured at 4°C or in the presence of 10 mM sodium azide (Sigma) [17]. In the latter experiments, MDCK-II were bathed on both sides with culture medium containing sodium azide for 30 min prior to and during apical exposure to 176 μg/mL PNP.…”