Developmental changes in multispecific organic anion transporter 1 expression in the rat kidney

Background. The cDNA of the multispecific organic anion transporter 1 (OAT1 ) responsible for the tubular secretion of organic anions was recently isol ated. In the current study, we investigated the developmental changes in OA T1 expression in the rat kidney. Methods. Ontogenic expression of rat OAT1 was investigated by Northern blot , in situ hybridization, Western blot, and immunohistochemical analysis. In addition, para-amino-hippurate (PAH) accumulation was measured using fetal , neonatal. and adult rat kidney slices. Results. In Northern blot analysis. OAT1 was detected as early as on embryo nic day 18 in the fetal kidney. The expression level of OAT1 mRNA increased remarkably just after birth (postnatal day 0). In situ hybridization revea led OAT1 expression on embryonic day 19. In both the fetal and neonatal kid neys, OAT1 mRNA was localized in a relatively deep region in the cortex. We stern blot analysis detected OAT1 protein on embryonic day 20. and the expr ession level increased after birth. Immunohistochemical analysis did not re veal OAT1 staining in the fetal kidneys. A faint signal of OAT1 protein was detected on postnatal day 0; thereafter, the expression level increased. T n the functional study using kidney slices, low but definite probenecid-sen sitive PAH accumulation was noted in fetal rat kidney on embryonic day 20. After birth. probenecid-sensitive PAH uptake was increased. Conclusions. The present study consistently demonstrates the remarkable inc rease of OAT1 expression after birth, and the immature excretory capacity o f the proximal tubules of the neonatal kidney can be attributed. at least i n part, to the low expression level of OAT1.