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 p ostprandial carboxyamidated and glycine-extended gastrin in the kidney s was 0.21 +/- 0.01 and 0.16 +/- 0.02, but the respective urinary clea rance 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 gly cine-extended gastrin-17 (gastrin-17 and gastrin-17Gly) during continu ous 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 tota l body clearance of gastrin-17. Renal filtration rate of gastrin-17 ex ceeded 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 o f the peptides (r = 0.93, P < 0.01). Neither was a renal plasma thresh old recorded nor was a T-m value for tubular uptake or degradation of gastrin achieved in spite of supraphysiological plasma levels of the p eptides. The results indicate that filtered gastrin is almost complete ly removed in the renal tubules, primary by metabolism although part o f the absorbed peptides may be returned to the circulation in intact f orm. The process for uptake or metabolism has a high capacity but vari es with the molecular form of gastrin.