title: The role of magnesium in regulating CCK-8-evoked secretory responses in the exocrine rat pancreas.
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 45 Ca2+ 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+.
authors.affiliation: Department of Applied Biology, University of Central Lancashire, England, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Wisdom
authors.forename: G M
authors.initials: GM
authors.lastname: Salido
authors.forename: L M
authors.initials: LM
authors.lastname: Baldwin
authors.forename: J
authors.initials: J
authors.lastname: Singh
mesh_terms: D000681:Amylases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology* / Q000502:physiology*; D008536:Meglumine / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D010189:Pancreatic Juice / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012844:Sincalide / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D013054:Spectrophotometry, Atomic; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; C049925:fura-2-am; D003994:Bucladesine; D008536:Meglumine; D012964:Sodium; D000681:Amylases; D008274:Magnesium; D012844:Sincalide; D002118:Calcium; D016257:Fura-2