Before weaning, arginine biosynthesis from citrulline most likely take
s place in the small intestine rather than in the kidney. We studied t
he expression of ornithine cycle enzymes in the rat small intestine du
ring perinatal development. The spatiotemporal patterns of expression
of ornithine aminotransferase, carbamoylphosphate synthetase, ornithin
e transcarbamoylase, argininosuccinate synthetase, argininosuccinate l
yase, and arginase mRNAs were studied by Northern blot analysis and in
situ hybridization. In addition, the expression of carbamoylphosphate
synthetase and argininosuccinate synthetase protein was studied by im
munohistochemistry. Before birth, the developmentally more mature prox
imal loops of the intestine expressed the mRNAs at higher concentratio
ns than the more distal loops. After birth, this difference was no lon
ger obvious. The mRNAs of argininosuccinate synthetase and argininosuc
cinate lyase, the enzymes that metabolize citrulline to arginine, were
detectable only in the upper part of the villi, whereas the other mRN
As were concentrated in the crypts. The distribution of argininosuccin
ate synthetase protein corresponded with that of the mRNA, whereas car
bamoylphosphate synthetase protein was present in all enterocytes of t
he crypts and villi. Hepatic arginase mRNA could not be detected in th
e enterocytes. The spatial distribution of the respective mRNAs and pr
oteins along the villus axis of the suckling small intestine indicates
that the basal enterocytes synthesize citrulline, whereas the enteroc
ytes in the upper half of the villus synthesize arginine.