Interaction between secretin and nerve-mediated amylase secretion in the isolated exocrine rat pancreas

This study investigates the effects of the gut peptide, secretin, on nerve-mediated and acetylcholine-evoked amylase secretion and calcium (Ca2+) and magnesium (Mg2+) mobilization in the in vitro rat pancreas. Both electrical field stimulation (EFS; 50 V, 20 Hz, 1 ms) and acetylcholine (ACh; 10(-6) M) caused marked increases in amylase output in isolated pancreatic segments. These responses were inhibited by atropine (10(-5) M). Secretin (10(-10) and 10(-8) M) evoked only a small increase in amylase secretion, which was unaffected by atropine. Combining either EFS or ACh with secretin resulted in an attenuation in amylase output compared with the response obtained with either EFS or ACh alone. In a Mg(2+)-free medium, secretin failed to inhibit the amylase output evoked by EFS. When forskolin (10(-5) M) was combined with EFS there was a marked potentiation of amylase output. In fura-2-loaded acinar cells, ACh (10(-6) M) elevated cytosolic free Ca2+ concentration ([Ca2+]i). Secretin alone had no detectable effect on [Ca2+]i compared with basal values, but it attenuated the ACh-induced elevation of [Ca2+]i. Both EFS and ACh elicited 45Ca2+ influx, whereas secretin had no significant effect. In the presence of secretin the EFS- and ACh-induced 45Ca2+ influx was reduced compared with responses obtained with either EFS or ACh alone. EFS caused a net efflux of Mg2+, whereas secretin alone evoked a net uptake of Mg2+ in pancreatic segments. Combining secretin with EFS resulted in a net uptake of Mg2+. In mag-fura-2-loaded acini ACh (10(-5) M) stimulated an initial transient rise in cytosolic free Mg2+ concentration ([Mg2+]i) followed by a sustained decrease in [Mg2+]i. Stimulation of acinar cells with secretin (10(-8) M) resulted in an elevation in [Mg2+]i compared with the resting level. When ACh (10(-5) M) was combined with secretin there was an initial increase in [Mg2+]i followed by a marked decrease to the pre-secretin-stimulated value. The results indicate that secretin may control nerve-mediated and ACh-evoked secretory responses in the rat pancreas, possibly by an interaction between cellular Ca2+ and Mg2+.