The metabolism of gastrin-52 and gastrin-6 in pigs

The kinetics and metabolism in various organs of three bioactive products o f progastrin, the small sulfated and nonsulfated gastrin-6 and the large no nsulfated gastrin-52, were examined during intravenous administration in an esthetized pigs. The kidney, hindlimb, liver, head, and gut eliminated the hexapeptides efficiently, with a fractional extraction ranging from 0.50 to 0.28 (P < 0.001-0.05). No metabolism was recorded in the lungs, and sulfat ion was without influence on the extraction of gastrin-6. Gastrin-52 was el iminated only in the kidney and the head, with a fractional extraction betw een 0.23 and 0.11 (P < 0.01-0.05). The half-life of sulfated and nonsulfate d gastrin-6 was 1.5 +/- 0.4 and 1.4 +/- 0.3 min, the metabolic clearance ra te (MCR) was 80.8 +/- 7.6 and 116.0 +/- 13.5 ml.kg(-1).min(-1) (P < 0.05), and the apparent volume of distribution (V-dss) was 199.3 +/- 70.1 and 231. 4 +/- 37.3 ml/kg, respectively. The decay of gastrin-52 in plasma was biexp onential. The half-lives of this biexponential after a bolus injection were 3.9 +/- 0.5 (T-1/2 alpha) and 25.7 +/- 1.4 (T-1/2 beta) min, and the MCR a nd V-dss were 4.2 +/- 0.4 ml.kg(-1).min(-1) and 116.2 +/- 16.2 ml/kg(1). We conclude that there is a differential elimination of progastrin products i n splanchnic and nonsplanchnic tissue, which depends on the chain length of the peptides. Sulfation of gastrin-6 had no influence on the organ-specifi c extraction but reduced the MCR. Our results are in keeping with previous studies of nonsulfated gastrin-17, which is extracted in the kidney, head, limb, and gut but not in the liver.