Stimulation of Gastric Acid Secretion in the Dog by the C-Terminal Penta-, Tetra-, and Tripeptides of Gastrin and their O-Methyl Esters

Acid secretion from the vagally innervated gastric fistula of conscious dogs was stimulated in a dose-related manner by the C-terminal penta-, tetra-, and tripetide amides of gastrin, the o -methyl esters of the tetra- and tripeptides, and the sulfone derivative of the tetrapeptide amide. The potency and efficacy of Peptavalon and the C-terminal penta- and tetrapeptide amides were about the same on a weight or molar basis. On a molar basis, the pentapeptide amide was about 4300 times as potent as the tripeptide amide. The o -methyl ester and the sulfone derivative of the tetrapeptide were about equipotent; they were, respectively, one-twenty-fifth and one-thirtieth as potent as the tetrapeptide amide. The dipeptide amides did not stimulate acid secretion in a dose range of 50 to 1500 µg per kg-hr. The results indicate that (1) the C-terminal tetrapeptide amide cannot be the minimal effective "stump" for biological activity in the gastrin molecule, (2) the C-terminal amide is important but not essential for gastric stimulating power, and (3) oxidation of the sulfur atom of the methionyl residue in the tetrapeptide does not result in total loss of activity.