De novo synthesis of pepsinogen was shown in isolated rabbit and human gastric glands after incubation of the glands in a 14C labelled amino acid enriched minimum Eagles medium. At regular intervals, glands and medium were separated and analysed by polyacrylamide gel electrophoresis. Newly synthesised pepsinogen was shown by autoradiography. Incorporation of 14C labelled amino acids was detected after only 30 min of culture and increased almost linearly in time for 4 h. By comparing the incorporation of label into total protein and into pepsinogen, it was concluded that pepsinogen formed 70-90% of the newly synthesised protein. Cimetidine, at a concentration of 160 micrograms/ml, strongly inhibited the synthesis of pepsinogen. Spontaneous secretion of pepsinogen into the medium was very low and relatively constant. Dibutyryl cyclic AMP considerably stimulated the secretion of pepsinogen into the medium. Histamine and pentagastrin did not influence the release of pepsinogen. These results show that isolated gastric glands are capable of synthesis and secretion of pepsinogen and that both can be selectively stimulated and inhibited.
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