Intestinal uptake of uridine in suckling rats: mechanism and ontogeny.
Nucleosides, essential substrates for a variety of intracellular metabolic reactions, are obtained from dietary and endogenous sources. Nucleotides (which dephosphorylate to nucleosides prior to intestinal absorption) are present in milk and have trophic effects on the developing gastrointestinal tract. The mechanism of transport of nucleosides in the developing intestine of suckling rats is unknown. To address this issue, we therefore examined uridine uptake in rat everted intestinal sacs. In suckling rats (15-17 days old), tissue uptake of low (5-microM) and high (60 microM) concentrations of [3H]-uridine was linear for up to 2 min of incubation. Initial rate of uptake of [3H]-uridine was (i) not significantly different in the jejunum and the ileum; (ii) greater in the presence of Na+, than other cations; (iii) saturable as a function of concentration with a Vmax of 21,044 +/- 2,302 pmol/g tissue wet wt/30 sec and an apparent Km of 33.8 +/- 10.1 microM; (iv) inhibited by high concentration (500 microM) of unlabeled uridine and other nucleosides; (v) temperature-dependent; (vi) energy-dependent; and (vii) pH-sensitive. Developmental maturation was associated with a progressive decrease in the Vmax of the uridine transport process (21,044 +/- 2,302, 14,651 +/- 1,679, and 8,461 +/- 1,369 pmol/g tissue wet wt/30 sec for suckling, weanling, and adult rats, respectively) and a progressive increase in the apparent Km of the uptake system (33.8 +/- 10.1, 55.6 +/- 13.1, and 61.7 +/- 14.5 microM for suckling, weanling, and adult rats, respectively). We concluded that uptake of uridine by the developing intestine of suckling rats involves a carrier-mediated system, which is energy- and temperature-dependent, and requires extracellular sodium. Furthermore, the uptake process was found to undergo clear ontogenic changes with maturation.
McCloud
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Department of Pediatrics, University of California-School of Medicine, Irvine 92668.
Mathis
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Grant
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Said
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D019297:2,4-Dinitrophenol; D000818:Animals; D000833:Animals, Suckling; D001386:Azides / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009705:Nucleosides / Q000494:pharmacology; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000494:pharmacology; D019810:Sodium Azide; D014475:Uncoupling Agents / Q000494:pharmacology; D014529:Uridine / Q000493:pharmacokinetics*
D001386:Azides; D004140:Dinitrophenols; D009705:Nucleosides; D014475:Uncoupling Agents; D019810:Sodium Azide; D012964:Sodium; D019297:2,4-Dinitrophenol; D014529:Uridine