PENETRATION ENHANCEMENT EFFECT OF PZ-PEPTIDE, A PARACELLULARLY TRANSPORTED PEPTIDE, IN RABBIT INTESTINAL SEGMENTS AND CACO-2 CELL MONOLAYERS

The objective of this study was to investigate the effect of Pt-peptid e -phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-D-Arg) on the permeabili ty of the rabbit intestinal segments and Caco-2 monolayers to hydrophi lic paracellular transport markers. Concentration-dependent penetratio n of Pz-peptide and Pz-peptide induced increase in the transport of pa racellular markers up to molecular radius 14 Angstrom were seen in bot h the lower intestinal segments and Caco-2 monolayers. In Caco-2 monol ayers, the increase in transport of paracellular markers with increasi ng Pz-peptide concentrations was correlated with the decrease in trans epithelial electrical resistance (TEER). Moreover, the decrease in TEE R induced by Pt-peptide, which was less prominent than that induced by equimolar concentrations of EDTA and cytochalasin B, was fully revers ible upon both short-and long-term exposure. Pz-peptide acted additive ly with EDTA and cytochalasin B to increase tight junctional permeabil ity. The above characteristics of Pz-peptide are consistent with those of an enhancer that is transient, reversible, and site-discriminant i n its action.