UPTAKE OF L-CARNITINE BY A HUMAN INTESTINAL EPITHELIAL-CELL LINE, CACO-2

Background & Aims: The mechanism of intestinal uptake of L-carnitine i s controversial, The aim of this study was to clarify the mechanism an d regulation of L-carnitine uptake, Methods: Uptake of [H-3]-L-carniti ne was measured across the apical membrane of confluent monolayers of Caco-2 cells, Results: [H-3]l-L-carnitine uptake was linear and apprec iable for up to 7 minutes with minimal metabolic alteration, was tempe rature- and Na+- (but not pH-) dependent, and included a saturable com ponent with an apparent Michaells constant of 45.5 +/- 6.5 mu mol/L an d maximum velocity of 83.5 +/- 5.6 nmol . mg protein(-1). 5 min(-1). U nlabeled L-carnitine and its structurally related analogues significan tly (P < 0.01) inhibited [H-3]-L-carnitine uptake, whereas unrelated c ompounds were ineffective. L-Carnitine uptake was also energy-dependen t, being significantly (P < 0.01) inhibited by metabolic inhibitors, O ur results also suggested that a calmodulin- but not a protein kinase C- or protein kinase A-mediated pathway plays a role in regulating L-c arnitine uptake by Caco-2 cells, Conclusions: L-carnitine uptake by In testinal epithelial cells (Caco-2) involves a carrier-mediated system that is temperature-, Na+-, and energy-dependent and seems to be under the regulation of a calmodulin-mediated pathway.