Second 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 45Ca2+ 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 fluorescent dye magfura, ACh and CCK-8 evoked marked reduction in cytosolic free Mg2+ concentration [Mg2+]i compared to the resting value of 0.82 +/- 0.03 mM (n = 50) in normal medium in the absence of secretagogues. In elevated [Mg2+]o (10 mM) medium, [Mg2+]i rises to 0.98 +/- 0.04 mM (n = 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.
Singh
J
J
Department of Applied Biology, University of Central Lancashire, Preston, England, UK.
Wisdom
D M
DM
D000109:Acetylcholine / Q000502:physiology; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D008274:Magnesium / Q000502:physiology*; D010179:Pancreas / Q000502:physiology*; D051381:Rats; D015290:Second Messenger Systems; D012636:Secretory Rate / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology; D012964:Sodium / Q000502:physiology; D013054:Spectrophotometry, Atomic
D012964:Sodium; D000681:Amylases; D008274:Magnesium; D012844:Sincalide; D000109:Acetylcholine; D002118:Calcium