Renal tubular transport and metabolism of carboxyamidated and glycine-extended gastrins in pigs.

Renal handling of postprandial and intravenously administered gastrin was investigated in anaesthetised pigs. The fractional extraction of postprandial carboxyamidated and glycine-extended gastrin in the kidneys was 0.21 +/- 0.01 and 0.16 +/- 0.02, but the respective urinary clearance comprised only 0.57 +/- 0.03 and 0.44 +/- 0.05% of the GFR (P < 0.02). The respective total body clearance of carboxyamidated and glycine-extended gastrin-17 (gastrin-17 and gastrin-17Gly) during continuous infusion was 22.9 +/- 1.5 and 19.6 +/- 1.4 mL kg-1 min-1 (NS), and the renal fractional extraction of the peptides was 0.31 +/- 0.03 and 0.29 +/- 0.05, respectively. The kidneys accounted for 8% of total body clearance of gastrin-17. Renal filtration rate of gastrin-17 exceeded renal extraction rate (9.739 +/- 0.487 vs. 6.407 +/- 0.321 pmol min-1). Urinary clearance of gastrin-17 and gastrin-17Gly amounted only 0.91 +/- 0.16 and 0.13 +/- 0.03%, respectively, of the GFR (P < 0.01), but urinary excretion rate correlated with the filtered amount of the peptides (r = 0.93, P < 0.01). Neither was a renal plasma threshold recorded nor was a Tm value for tubular uptake or degradation of gastrin achieved in spite of supraphysiological plasma levels of the peptides. The results indicate that filtered gastrin is almost completely removed in the renal tubules, primary by metabolism although part of the absorbed peptides may be returned to the circulation in intact form. The process for uptake or metabolism has a high capacity but varies with the molecular form of gastrin.