Pepsinogens I and II: Purification from gastric mucosa and radioimmunoassay in serum

Abstract

Pepsinogen I and pepsinogen II were purified from gastric mucosa and used to develop a radioimmunoassay for pepsinogen II and an improved radioimmunoassay for pepsinogen I. Each immunochemically homogeneous preparation contained only its characteristic components by radioelectophoretic analysis, and migrated as a single band in polyacrylamide gel. The mean (±SD) level of serum pepsinogen II in 42 healthy control subjects was 10.8 ± 3.8 ng/ml, significantly less (p < 0.001) than the level of pepsinogen I, which was 62.9 ± 22.2 ng/ml. The correlation between serum pepsinogen I and pepsinogen II was highly significant (r = 0.700, p < 0.001) in these subjects. In 20 patients with pernicious anemia the mean serum pepsinogen II level was 10.6 ± 2.5 ng/ml, not different from normal, but significantly higher (p < 0.001) than the level of pepsinogen I which was 5.9 ± 4.7 ng/ml. In 10 patients with total gastrectomy, serum pepsinogen I was 3.9 ± 3.1 ng/ml and serum pepsinogen II was 3.2 ±3.1 ng/ml; both values were significantly lower (p < 0.001) than the corresponding levels in pernicious anemia. The predominance of pepsinogen I in the serum of healthy control subjects suggests that either the gastric chief cell normally releases more pepsinogen I than pepsinogen II into the circulation or that pepsinogen I has a longer metabolic clearance rate than pepsinogen II. The marked decrease in serum pepsinogen I in patients with pernicious anemia is best explained by a loss of gastric chief cells due to severe atrophic gastritis of the fundic glands. The normal distribution of serum pepsinogen II levels in these patients may reflect an increased number of pyloric glands due to pyloric gland metaplasia of the proximal stomach.