STUDY OF THE MECHANISM OF PEPSINOGEN SECRETION.

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To investigate the mechanism of pepsinogen secretion (PS), the three lines of studies have been done, and the following results were obtained.(1) The effects of agonists and intracellular messengers on the PS was observed in isolated frog pepsinogen acini. Adrenergic, cholinergic and bombesin stimulation caused dose-related increase in PS, and the latter two of them caused the increase in [Ca^<2+>]i simultaneously. DBcAMP, TPA and A23187 caused dose-related increase in pepsinogen secretion, any combination of the secretagogues caused additive or potentiative interaction in PG. The results suggest that the mechanism of PS involves three messenger pathways; cAMP, [Ca^<2+>]i and protein kinase C, and that [Ca^<2+>]i play a important role in the development of desensitization.(2) K^+ channels and cellar electrical potential were observed in the isolated frog oxyntic cells. The most frequent observed channels had a unit conductance 30-35 pS which was activated by DBcAMP and histamine. The higher conductance 55-60 PS channel was activated by cholinergic stimulation and Ca^<2+> ionophore. These channels were both highly selective for K^+. The magnitude of currents was reduced by Mg^<2+>. The two K^+ channels were inhibited by omeprazole. These results indicate that the K^+ channels are regulated by the secretagogues and intracellar messengers, and may be responsible for maintenance of membrane potential.(3) Omeprazole increased PS in both experimental and clinical observation. The effect of omeprazole may be not involve in the function of membrane receptors.