PT  - JOURNAL ARTICLE
AU  - J H Hochman
AU  - J A Fix
AU  - E L LeCluyse
TI  - In vitro and in vivo analysis of the mechanism of absorption enhancement by palmitoylcarnitine.
DP  - 1994 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 813--822
VI  - 269
IP  - 2
4099  - http://jpet.aspetjournals.org/content/269/2/813.short
4100  - http://jpet.aspetjournals.org/content/269/2/813.full
SO  - J Pharmacol Exp Ther1994 May 01; 269
AB  - Long-chain acylcarnitines (12-18 carbon fatty acid esters) dramatically enhance the absorption of hydrophilic drugs across intestinal mucosa without altering the morphology of the epithelium. The mechanism underlying these effects was studied using the colon carcinoma cell line Caco-2. Caco-2 monolayers treated with 0.2 mM palmitoylcarnitine (PCC) show dramatic increases in the transport of hydrophilic markers. This enhanced transport coincides with a rapid drop in transepithelial electrical resistance (TER). The drop in TER is initiated within the first minute after PCC addition and continues for approximately 20 min to a 70 to 85% drop of the initial TER values. This effect is reversible after removing the PCC and does not appear to involve lysis of the apical membrane. Instead PCC's effect appears to be due to loosening of tight junctions as indicated by the accumulation of fluorescent dextrans and the electron dense marker lanthanum nitrate in paracellular spaces. Moreover transmission electron microscopy and freeze fracture electron microscopy indicate that PCC produces significant structural alterations to tight junctions. In contrast to many other tight junction disrupting agents, PCC effects appear to be Ca(++)-independent and PCC does not induce significant disruption of actin filament distribution in Caco-2 cells.