Mechanisms of acylcarnitine-mediated enhancement of calcium transport in the Caco-2 cell monolayer model.
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) loosening 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 reversal 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 calcium transport by acylcarnitines. Calmidazolium, a potent Ca-ATPase pump inhibitor in tissues such as rat intestinal segments, failed to inhibit this pump in Caco-2 cells. Thus, the predominant mechanism of enhancement of calcium transport by acylcarnitines in the Caco-2 model appears to be via promotion of paracellular transport.
Surendran
N
N
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Nguyen
L D
LD
Giuliano
A R
AR
Blanchard
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002331:Carnitine / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D009543:Nifedipine / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D002331:Carnitine; D002118:Calcium