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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.

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.

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