A creatine transporter is operative at the brush border level of the rat jejunal enterocyte

Although ergogenic effects and health benefits have been reported for creatine used as nutritional supplement, to date little is known about the mechanism of creatine absorption in the small intestine. Thus the current study was undertaken to elucidate the mechanism of creatine intake in rat jejunum with the use of well-purified brush border membrane vesicles, isolated from jejunal enterocyte. Creatine uptake was found markedly stimulated by inwardly directed Na+ and Cl- gradients, potential-sensitive, strongly reduced by the substitution of Na+ and Cl- with various cations and anions and positively affected by intravesicular K+. Moreover creatine uptake is: 1) significantly inhibited by creatine stuctural analogs, 2) abolished by low concentrations of MTSEA, 3) saturable as a function of creatine concentration with an apparent Michaelis-Menten costant of 24.08 ± 0.80 mM and a maximal velocity of 391.30 ± 6.19 pmoles mg protein-1 30 s-1. The transport is electrogenic since at least two Na+ and one Cl- are required to transport one creatine molecule. Western blot analysis showed the same amount of creatine transport protein in the jejunal apical membrane when compared to ileum. Thus these data demonstrate the existence of a Na+- and Cl--dependent, PD-sensitive, electrogenic carrier-mediated mechanism for creatine absorption in rat jejunal apical membrane vesicles, which is biochemically and pharmacologically similar to those observed in other tissues. However in other cell types the stimulatory effect of intravesicular K+ was never detected.