The role of magnesium in regulating CCK-8-evoked secretory responses in the exocrine rat pancreas |
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Authors: | Denham M Wisdom Gines M Salido Lisa M Baldwin Jaipaul Singh |
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Institution: | (1) Cell Communication Group, Department of Applied Biology, University of Central Lancashire, PR1 2HE Preston, England, UK;(2) Department of Physiology, Faculty of Veterinary Sciences, University of Extramadura, 10800 Caceres, Spain |
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Abstract: | This study investigates the effect of magnesium (Mg2+) on the secretory responses and the mobilization of calcium (Ca2+) and Mg2+ evoked by cholecystokinin-octapeptide (CCK-8) in the exocrine rat pancreas. In the isolated intact perfused pancreas CCK-8 (10–10 M) produced marked increases in juice flow and total protein output in zero and normal (1.1 mM) extracellular Mg2+ Mg2+]o compared to a much reduced secretory response in elevated (5 mM and 10 mM) Mg2+]o Similar effects of perturbation of Mg2+]o on amylase secretion and 45Ca2+ uptake (influx) were obtained in isolated pancreatic segments. In pancreatic acinar cells loaded with the fluorescent bioprobe fura-2 acetomethylester (AM), CCK-8 evoked marked increases in cytosolic free Ca2+ concentration Ca2+]i in zero and normal Mg2+]o compared to a much reduced response in elevated Mg2+]o Pretreatment of acinar cells with either dibutyryl cyclic AMP (DB2 cAMP) or forskolin had no effect on the CCK-8 induced changes in Ca2+]i. In magfura-2-loaded acinar cells CCK-8 (10–8 M) stimulated an initial transient rise in intracellular free Mg2+ concentration Mg2+]i followed by a more prolonged and sustained decrease. This response was abolished when sodium Na+ was replaced with N-methyl-D-glucamine (NMDG). Incubation of acinar cells with 10 mM Mg2+ resulted in an elevation in Mg2+]i. Upon stimulation with CCK-8, Mg2+]i. decreased only slightly compared with the response obtained in normal Mg2+]o. CCK-8 caused a net efflux of Mg2+ in pancreatic segments; this effect was abolished when extracellular sodium Na+]o was replaced with either NMDG or choline. The results indicate that Mg2+ can regulate CCK-8-evoked secretory responses in the exocrine pancreas possibly via Ca2+ mobilization. Moreover, the movement of Mg2+ in pancreatic acinar cells is dependent upon extracellular Na+. |
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Keywords: | rat pancreas cholecystokinin-octapeptide magnesium calcium secretion cyclic AMP |
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