Mechanism of action of magnesium on acetylcholine‐evoked secretory responses in isolated rat pancreas

This study investigates the effects of magnesium (Mg2+) on acetylcholine (ACh)‐evoked secretory responses and calcium (Ca2+) mobilization in the isolated rat pancreas. ACh induced marked dose‐dependent increases in total protein output and amylase release from superfused pancreatic segments in zero, normal (1 x 1 mM) and elevated (10 mM) extracellular Mg2+. Elevated Mg2+ attenuated the ACh‐evoked secretory responses compared to zero and normal Mg2+. In the absence of extracellular Ca2+, but presence of 1 mM‐EGTA (ethylene glycol bis(beta‐aminoethylether)‐N,N,N',N''‐tetraacetic acid), ACh elicited a small transient release of protein from pancreatic segments compared to a larger and more sustained secretion in the absence of both Ca2+ and Mg2+. Incubation of pancreatic segments with 45Ca2+ resulted in time‐dependent uptake with maximum influx of 45Ca2+ occurring after 20 min of incubation period. ACh stimulated markedly the 45Ca2+ uptake compared to control tissues. In elevated extracellular Mg2+ the ACh‐induced 45Ca2+ influx was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. ACh also evoked dose‐dependent increases in cytosolic free Ca2+ concentrations ([Ca2+]i) in pancreatic acinar cells loaded with the fluorescent dye Fura‐2 AM. In elevated Mg2+ the ACh‐induced cytosolic [Ca2+]i was significantly (P less than 0.001) reduced compared to zero and normal Mg2+. These results indicate that Mg2+ can influence ACh‐evoked secretory responses possibly by controlling both Ca2+ influx and release in pancreatic acinar cells.