Hepatic inactivation of gastrins of various chain lengths in dogs.

In dogs with gastric fistulae and with transposition of the portal vein and the inferior vena cava, we studied secretion of acid in response to portal or systemic venous infusion of a series of progressively longer fragments of the carboxyl terminal portion of human gastrin. Pentagastrin, G6, G7, G8, G9, G10, G13, G17, and G34 were studied. Potency by portal venous infusion relative to systemic venous infusion was used as an index of hepatic inactivation. Fragments with eight or fewer amino acid residues were more than 90% inactivated by hepatic transit. Fragments with nine or more amino acid residues were more resistant to hepatic inactivation than shorter fragments. For fragments with 7 to 17 amino acid residues, increasing the chain length was accompanied by progressive increase both in hepatic resistance to inactivation and in potency for stimulation of acid secretion, suggesting that resistance to hepatic inactivation may be a major determinant of potency.