Effects of peptide hormone structure on H+ secretion by Necturus gastric mucosa.
The actions of human synthetic gastrin I(G), the C-terminal tetrapeptide of gastrin (T), and the C-terminal octapeptide of cholecystokinin (OP) on acid secretion and transepithelial potential difference (PD) of the isolated Necturus gastric mucosa were determined. All three peptides induced H+ secretion, but the maximum H+ output was less with OP than with G or T. G and OP produced their maximum H+ output at lower molar concentrations than T. G- and OP-stimulated secretion was long sustained, but T-stimulated secretion rapidly returned to basal levels. T- and G-stimulated secretion was partially inhibited by the addition of OP. Evidence is presented that T rapidly disappears from solutions exposed to gastric mucosa, whereas G does not. Washing sensitized the mucosa to subsequent addition of T. The results suggest that the action of the common C-terminal tetrapeptide of G, T, and OP is modified by the preceding amino acid sequences, and that T, the smallest of the three peptides, is rapidly degraded by gastric tissue in vitro. The implications of the work for the study of gastrointestinal hormone structure-function relationships in isolated tissue preparations are discussed.
D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D014562:Caudata / Q000378:metabolism*
D005755:Gastrins; D010446:Peptide Fragments; D002766:Cholecystokinin