DEVELOPMENTAL REGULATION OF CHLORIDE FORMATE EXCHANGE IN GUINEA-PIG PROXIMAL TUBULES/

There is a marked decrease in renal NaCl excretion immediately followi ng birth. To test the hypothesis that parallel upregulation of the pro ximal tubule apical membrane Na+/H+ and Cl-/formate exchangers contrib utes to this postnatal adaptation, we measured exchanger activities in brush-border membrane vesicles from near-term fetal, 3- to 5-day-old, and adult guinea pigs. Uptake of Cl-36(-) was measured in the presenc e of an outwardly directed formate gradient and an inwardly directed p roton gradient. In other experiments, Na-22(+) uptake was measured in the presence of an outwardly directed proton gradient. Cl-36(-) uptake was inhibitable by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid ( DIDS) and furosemide, and Na-22(+) uptake was inhibitable by amiloride . Maximal uptakes of both Cl-36(-) and Na-22(+) exceeded 2-h equilibra tion values in vesicles from newborn and adult guinea pigs, suggesting transporter-mediated uptake. Such overshoots were not seen with the v esicles from fetuses. Compared with vesicles from fetuses, the initial velocity of formate-driven Cl-36(-) uptake was 73% greater in vesicle s from newborns and 65% greater in vesicles from adults. These results demonstrate parallel upregulation of proximal tubule Na+/H+ and Cl-/f ormate exchanger activities immediately after birth. This parallel upr egulation may be important in mediating the postnatal decrease in rena l NaCl excretion.