Abstract
Regulation mechanisms of pepsinogen (EC 3.4.23.) synthesis and secretion were studied by following newly synthesized [ 14C]-labeled pepsinogen during culture of isolated rabbit gastric glands. Omeprazole, a substituted benzimidazole, while almost completely abolishing acid production at 10 −4M, strongly stimulated secretion of preformed and newly synthesized pepsinogen. Although the pepsinogen synthesis at this concentration of omeprazole was reduced to about 55% of the control rate, a two-fold absolute increase of total secreted pepsinogen was found. This increase was not due to a non specific leakage through disruption of chief cell membranes, as no increase of lactate dehydrogenase in the culture medium could be demonstrated. The stimulated secretion was influenced neither by 10 −3 M cimetidine, 10 −3 M sodium thiocyanate nor 10 −4 M atropine. No additivity was found between the carbachol (10 −4 M) or dibutyryl cyclic AMP (10 −3 M) and the omeprazole induced pepsinogen secretion.
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