Tubular handling of pepsinogen A and C in man: evidence for two distinct tubular reabsorption mechanisms for low molecular weight proteins in man.
Pepsinogen A (PGA) and Pepsinogen C (PGC) are circulating low-molecular-weight proteins. Both have been shown to be almost freely filtered through the glomerular basement membrane. In man, only PGA is present in significant amounts in the urine. This prompted us to investigate the tubular reabsorption of PGA and PGC in man. Fifty-eight 24-hour urine specimens and a serum samples were obtained from 21 healthy subjects. Eight serum and urine samples were obtained after raising the serum PGA and PGC levels by oral administration of omeprazole. Filtered loads of PGA and PGC and tubular reabsorptions were calculated. PGA was already present in the urine at filtered loads below the tubular reabsorption maximum (10.6 +/- 3.5 mg/24 h; mean +/- SD) that was reached at serum PGA levels above 66 micrograms/l. Furthermore, intraindividual variation in tubular reabsorption of PGA was observed. Urinary excretion of PGC remained very low and the tubular reabsorption maximum for PGC was not reached. These data show that the presence of large amounts of PGA in the urine of healthy volunteers is due to a low affinity of the tubules for PGA. Tubular affinity of PGA changes in time and factors responsible for these changes require further investigation. The absence of PGC from the urine is due to a high affinity of the tubules for PGC and a high capacity compared to normal filtered loads. The similarity between PGA and PGC molecules suggests that minor differences in molecular structure can be responsible for large differences in tubular reabsorption.
ten Kate
R W
RW
Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
Pals
G
G
Donker
A J
AJ
Pronk
J C
JC
Meuwissen
S G
SG
D000042:Absorption; D000328:Adult; D005260:Female; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009853:Omeprazole / Q000378:metabolism; D010435:Pepsinogens / Q000378:metabolism*
D010435:Pepsinogens; D009853:Omeprazole