Developmental maturation and segmental distribution of rat small intestinal L-carnitine uptake.
Oral L-carnitine supplementation is commonly used in sports nutrition and in medicine; however, there is controversy regarding the mechanisms that mediate intestinal L-carnitine transport. We have previously reported that the Na(+)/L-carnitine transporter OCTN2 is present in the small intestinal apical membrane. Herein we aimed to find out if this step of intestinal L-carnitine absorption is ontogenically regulated, and if so, to determine the molecular mechanism(s) involved. L-[(3)H]-Carnitine uptake was measured in the jejunum and ileum of fetuses (E17 and E21), newborn (1 day-old), suckling (15 day-old), weaning (1 month-old) and adult (2 and 6 month-old) Wistar rats. Both, Na(+) -dependent and Na(+) -independent L-carnitine uptake rates, normalized to intestinal weight, significantly increased during the late gestation period, and then declined during the suckling period. After weaning, the rate of Na(+) -dependent L-carnitine uptake is no longer measurable. In E21- fetuses and newborn rats, L-carnitine uptake was higher in the ileum than in the jejunum. The decline in Na(+) -dependent L-carnitine uptake with maturation was mediated via a decrease in the V(max) of the uptake process with no change in its apparent K(m). Semi-quantitative RT-PCR assays showed that OCTN2 mRNA levels were significantly higher in E21-fetuses and newborn rats compared to suckling rats, which were in turn significantly higher than that in adult rats. Neither retardation of weaning nor L-carnitine supplementation prevented the down-regulation of Na(+)/L-carnitine transport activity. The results demonstrate for the first time that intestinal Na(+) -dependent L-carnitine uptake activity is under genetic regulation at the transcriptional level.
García-Miranda
P
P
Depto. Fisiología y Zoología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Durán
J M
JM
Peral
M J
MJ
Ilundáin
A A
AA
D000284:Administration, Oral; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002331:Carnitine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000196:embryology* / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism*; D000074058:Solute Carrier Family 22 Member 5; D014018:Tissue Distribution
D027701:Organic Cation Transport Proteins; C115441:Slc22a5 protein, rat; D000074058:Solute Carrier Family 22 Member 5; D012964:Sodium; D002331:Carnitine