Cellular messengers of stimulants of pepsinogen secretion from isolated frog esophageal mucosa

Abstract

The messenger roles of Ca2+ and cyclic nucleotides in the stimulation of pepsinogen secretion by three classes of stimuli [muscarinic (bethanechol), peptidergic (bombesin), and adrenergic (isoproterenol)] were studied in vitro using the peptic gland-bearing esophageal mucosa from the American bullfrog, Rana catesbeiana. Pepsinogen secretion was stimulated in a dose-dependent manner by the calcium ionophore A23187, by dibutyryl cAMP (DBcAMP), and by isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor. Isoproterenol and bethanechol increased the tissue cAMP content in the presence of IBMX. IBMX, which by itself stimulated secretion, was potentiating in combination with bombesin, additive with bethanechol, and less than additive with isoproterenol. Omission of Ca2+ from the bathing medium did not alter basal pepsinogen secretion nor the response to maximally effective doses of isoproterenol but partly inhibited the secretory responses to bethanechol and bombesin. Ca2+-free medium with 1 mM EGTA reduced pepsinogen secretion under all basal and stimulated (including A23187- but not DBcAMP-stimulated) conditions, indicating a critical role for Ca2+ in the secretion of pepsinogen secretion. A23187 by itself produced only an initial (15-20 min) release of pepsinogen, whereas IBMX and DBcAMP produced a delayed sustained secretion. The combination of A23187 with either IBMX or DBcAMP mimicked the responses to bethanechol or bombesin. These results indicate that both calcium and cAMP may be obligatory and interacting intermediates in the full stimulation of pepsinogen secretion by frog esophageal peptic glands with at least cholinergic and peptidergic stimuli.