Tubular reabsorption of pepsinogen isozymogens in man studied by the inhibition of tubular protein reabsorption with dibasic amino acids.

1. The fractional clearances of pepsinogen A (PGA), pepsinogen C (PGC) and the main PGA isozymogens, i.e. PGA-3, PGA-4 and PGA-5, were measured in 13 healthy male volunteers before and during blockade of tubular protein reabsorption by intravenous infusion of either L-arginine hydrochloride (n = 8; 0.5 g h-1 kg-1 body weight) or an equimolar amount of L-lysine hydrochloride (n = 5; 0.44 g h-1 kg-1 body weight). Glomerular filtration rate was measured by a radioisotope method. 2. The fractional baseline clearance of PGC (1 +/- 1%) was lower than that of PGA (20 +/- 10%). In addition, the fractional clearance of the PGA isozymogens appeared to be different: the fractional clearance of PGA-5 (7 +/- 3%) was lower than that of PGA-4 (18 +/- 9%), and the fractional clearance of PGA-4 was lower than that of PGA-3 (30 +/- 10%). These differences in fractional clearance between PGA isozymogens decreased during infusion of both arginine and lysine. 3. Pepsinogens are freely filtered proteins. It can therefore be concluded that the differences in fractional clearance between PGA isozymogens imply differences in tubular reabsorption. This is remarkable as PGA isozymogens are proteins with an almost identical amino acid sequence and electric charge. The disappearance of the differences in tubular reabsorption during arginine and lysine infusion suggests that PGA isozymogens differ in affinity for negatively charged binding sites in the tubular cell membrane. In order to explain the low fractional clearance of PGC compared with that of PGA and the less marked effect of arginine or lysine infusion on the fractional clearance of PGC, an additional PGC-specific binding site has to be postulated.