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The basal concentrations of sulfated and non-sulfated gastrins in serum were measured radioimmunochemically in healthy subjects and in normo- and hyper-gastrinemic diseases. The degree of sulfation in patients with duodenal and gastric ulcer, chronic pancreatitis, gallstone disease, and chronic renal failure were similar to that of healthy controls, in whom 37.7 +/- 1.9% (mean +/- SEM) of serum gastrins were sulfated. In eight patients with the Zollinger-Ellison syndrome 57 +/- 5.4% of the gastrins were sulfated (p less than 0.005, compared with controls). In patients with pernicious anemia (no. = 20) only 24.4 +/- 2.0% of the gastrins were sulfated (p less than 0.005, compared with controls). An inverse correlation (r = -0.63, p less than 0.01) was found between the degree of sulfation and the total gastrin concentration in pernicious anemia but not in gastrinoma patients. The results indicate that diseases with increased synthesis of gastrin are accompanied by an abnormal degree of sulfation.

Gastrin 17 (G17) is a potent stimulant of gastric acid secretion in vivo. In this study, the effects of G17 and some related peptides on intracellular free Ca2+ in isolated pig parietal cells were studied. Both G17 and the synthetic peptide pentagastrin increased intracellular free Ca2+ in a dose-dependent manner over the concentration range 10(-9) to 10(-6) M, suggesting a specific action. The EC50 values were 3 X 10(-8) M for G17 and 8 X 10(-8) M for pentagastrin. The N-terminal tridecapeptide of G17 [(1-13)G17] did not have any effect on intracellular free Ca2+, nor was it able to inhibit the action of G17. A glycine-extended gastrin [(5-17)G17-Gly)] elicited a small but significant increase in intracellular free Ca2+ although only at 10(-6) M. This increase was approximately 20% of that obtained with a similar concentration of G17. Sequential incubations with (5-17)G17-Gly and G17 showed that both peptides increased the intracellular free Ca2+ through the same mechanisms.

The effect of sulfuric acid esterification of Tyr-12 in gastrin-17 on immunoreactivity was evaluated by the ability of seventeen antisera raised against non-sulfated gastrin-17 to bind sulfated gastrins in extracts of gastrinoma and antral tissue. Using non-sulfated Tyr-12 iodinated gastrin as tracer, and non-sulfated gastrin-17 as standard the antisera showed three different patterns of reactivity: Three antisera (Nos. 2602, 2605 and 4562) bound sulfated gastrins with low (4-23%) potency; four antisera (Nos. 2604, 2720, 4710 and 4713) measured sulfated gastrins with a potency similar to that of non-sulfated gastrins (81-100% crossreactivity); whereas ten antisera (Nos. 2601, 2606, 2609, 2716, 2717, 2718, 4556, 4559, 4560 and 4563) displayed enhanced reactivity with sulfated gastrins (130-373% crossreactivity). Using Gly-2 iodinated gastrin as tracer, the latter type of antisera reacted almost equally with sulfated and non-sulfated gastrins, suggesting that the apparent increase in binding of sulfated gastrins rather is due to increased displacement of Tyr-12 iodinated gastrin. The results show that derivatization of amino acid residues greatly influences antibody binding.