N. Surendran et al., MECHANISMS OF ACYLCARNITINE-MEDIATED ENHANCEMENT OF CALCIUM-TRANSPORTIN THE CACO-2 CELL MONOLAYER MODEL, Journal of pharmaceutical sciences, 84(3), 1995, pp. 269-274
The overall objective of this study was to determine the mechanisms of
acylcarnitine-mediated enhancement of calcium transport across Caco-2
cells. The different mechanisms of enhancement postulated are (a) loo
sening of tight junctions, thereby promoting paracellular transport; (
b) opening of calcium channels, thus increasing calcium entry; and (c)
stimulation of the basolateral Ca-ATPase pump, thereby aiding calcium
extrusion. Although the existence of calcium channels and the reversa
l of verapamil-mediated inhibition of calcium uptake by acylcarnitines
were demonstrated for the first time in Caco-2 cells, the channels do
not appear to be a major contributing factor to the enhancement of ca
lcium transport by acylcarnitines. Calmidazolium, a potent Ca-ATPase p
ump inhibitor in tissues such as rat intestinal segments, failed to in
hibit this pump in Caco-2 cells. Thus, the predominant mechanism of en
hancement of calcium transport by acylcarnitines in the Caco-2 model a
ppears to be via promotion of paracellular transport.