MOLECULAR WEIGHT-DEPENDENT PARACELLULAR TRANSPORT OF FLUORESCENT MODEL COMPOUNDS INDUCED BY PALMITOYLCARNITINE CHLORIDE ACROSS THE HUMAN INTESTINAL EPITHELIAL-CELL LINE CACO-2

Long-chain acylcarnitines, such as palmitoylcarnitine chloride (PCC), are endogenous compounds which have been shown to increase intestinal transport of small hydrophilic compounds (including some pharmaceutica l agents) through the paracellular pathway. However, the size range of the compounds whose absorption can be improved by PCC has not been fu lly investigated. In the present study, we systematically examined the effect of PCC on the transport rate of a series of hydrophilic fluore scent model compounds of varying molecular weights (0.3-71.2 kD) acros s cultured monolayers of the human intestinal epithelial cells Caco-2. Mucosal addition of 100 or 200 mu M PCC resulted in comparable time-d ependent decreases in the transepithelial electric resistance (T-1/2, similar to 15 min). PCC addition induced a striking increase in the tr ansport of sodium fluorescein (Flu-Na; 0.3 kD) and a slight or moderat e increase in transports of fluorescent compounds of 0.6- 11 kD, Th; e ffect of PCC on transport of compounds with molecular weights of great er than or equal to 17 kD appeared to be negligible. Examination by co nfocal laser scanning microscopy clearly revealed dilated paracellular spaces in Caco-2 monolayers which had been mucosally pretreated with PCC, confirming that PCC increases intestinal permeability by opening a paracellular transport pathway. Our results suggest that PCC is part icularly effective in enhancing intestinal absorption of small hydroph ilic compound like Flu-Na and may also have limited use in promoting t he transport of compounds of less than or equal to 10 kD.