2ND-MESSENGER ROLE OF MAGNESIUM IN PANCREATIC ACINAR-CELLS OF THE RAT

Application of either acetylcholine (ACh,10(-5) M) or cholecystokinin-octapeptide (CCK-8, 10(-8) M) to the isolated rat pancreas elicited large increases in amylase secretion, radiolabelled Ca-45(2+) influx and cytosolic free calcium [Ca2+](i) levels in zero and normal (1.1 mM) extracellular magnesium [Mg2+](o). Elevated [Mg2+](o) significantly (p < 0.001) reduced the secretagogue-evoked secretory responses and Ca2+ mobilisation. Stimulation of pancreatic segments with either ACh (10(-5) and 10(-6) M) or CCK-8 (10(-8) and 10(-10) M) resulted in marked elevation in Mg2+ concentration in effluent samples (net efflux). On removal of either ACh or CCK-8, Mg2+ concentration returned to resting level. In pancreatic acinar cells loaded the flourescent dye magfura, ACh and CCK-8 evoked marked reduction in cytosolic free Mg2+ concentration [Mg2+](i) compared to the resting 50) in normal medium in the absence of secretagogues. In elevated [Mg2+](o) (10 mM) medium, 6). Addition of CCK-8 led to only a small reduction in [Mg2+](i) in elevated [Mg2+](o). In Mg2+ loaded pancreatic acinar cells, Mg2+ is released in a time dependent manner and this efflux of Mg2+ was sensitive to sodium, extracellular amiloride (1 mM), dinitrophenol (10 mM) and lidocaine (1 mM). The results indicate that Mg2+ is acting as an intracellular messenger to regulate the mobilisation of Ca2+ which in turn mediates enzyme secretion.