Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.
Acid-stimulating action and clearance of pure natural human big gastriin (HG-34-I) and little gastrin (HG-17-I) were assessed in four male subjects with inactive duodenal ulcer (DU) disease. Disappearance half-times for HG-17-I after intravenous infusion (5.2 min) or rapid intravenous injection (6.4 min) were six to eight times shorter than those for HG-34-I (41.5 and 37.8 min, respectively). Studies of clearance of synthetic human little gastrin (HG-17-I) were performed in three of these same four DU subjects, eight additional male DU subjects, and eleven normal male subjects. The disappearance halftime of synthetic HG-17-I averaged 6.2 min in both the DU subjects and the normal subjects. These data suggest that clearance of exogenous gastrin is not altered in patients with DU. Acid secretion in response to rapid intravenous injection of HG-34-I reached a higher peak and lasted longer than in response to an equimolar dose of HG-17-I; the total response to HG-34-I was about three times that to HG-17-I. During constant intravenous infusion, acid responses to equimolar exogenous doses of the two peptides were similar but the increment in molar concentration of circulating gastrin was six to eight times greater with HG-34-I than with HG-17-I. Chromatography of serum obtained during infusions of HG-34-I revealed no evidence of conversion to HG-17-I, nor was there any increase in circulating G-34 activity during infusions of HG-17-I. The increment in serum gastrin concentration required to produce half-maximal stimulation of gastric acid secretion (D50) was estimated in each subject for each gastrin from curves relating acid secretion to change in serum gastrin concentration produced by infusion of these peptides. After instilling peptone solution into the stomach, acid secretion was measured by intragastric titration, and increases in circulating G-17 and G-34 were determined by chromatography and radioimmunoassay of serum. Increases in circulating G-17 and G-34 in response to the peptone meal, taken together, were equivalent to 1.5 times the D50 determined from infusions of G-34 and G-17. Acid secretion during the same time period averaged 55% of maximal rates. Although G-34 comprised approximately three-fourths of the total molar concentration of circulating gastrin after stimulation, it was estimated to contribute less than half of the acid-stimulating activity.
D004305:Dose-Response Relationship, Drug; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000378:metabolism*; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011863:Radioimmunoassay
D005755:Gastrins