Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture.
Recently, glycine-extended processing intermediates of progastrin were identified in porcine stomach using a radioimmunoassay with conventional polyclonal antisera developed against a synthetic peptide analogue for progastrin processing intermediates, gastrin 6-G(Tyr-Gly-Trp-Met-Asp-Phe-Gly). We developed monoclonal antibodies specific for glycine-extended processing intermediates of progastrin (gastrin G). Monoclonal antibody 109-21 appeared to require the carboxyl-terminal pentapeptide structure of gastrin 6-G for maximal binding. Cross-reactivities of 109-21 against gastrin 17 I, gastrin 17 II, cholecystokinin-octapeptide, des(SO3) cholecystokinin-octapeptide, and gastrin 6-G-R-R were respectively 1%, less than 0.1%, less than 0.1%, 0.1%, and 0.5%. With this monoclonal antibody and a polyclonal gastrin antibody we examined the concentrations of gastrin and gastrin G in tissue and the effects of bombesin on the release of gastrin and gastrin G from rat antral mucosa in tissue culture. The gastrin G to gastrin ratio was 2.2 in rat antral mucosa and 0.66 in rat duodenal mucosa. In tissue culture, bombesin significantly stimulated gastrin and gastrin-G secretion at doses of 10(-8) and 3 X 10(-8) M. Atropine (10(-6) M) abolished the actions of carbachol to stimulate gastrin and gastrin-G secretion but had no effect on bombesin-stimulated gastrin and gastrin-G secretion. These results suggest that gastrin G is cosecreted with gastrin in response to carbachol and bombesin, and the stimulation of gastrin and gastrin-G secretion by bombesin does not involve cholinergic neural pathways and may reflect a direct action on gastrin cells.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D001839:Bombesin / Q000494:pharmacology*; D002850:Chromatography, Gel; D003429:Cross Reactions; D046508:Culture Techniques; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D000911:Antibodies, Monoclonal; D005755:Gastrins; D011498:Protein Precursors; C013706:big gastrin; D001839:Bombesin