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. 1987 Mar;84(5):1282–1285. doi: 10.1073/pnas.84.5.1282

Modulation of cytosolic free calcium levels by extracellular phosphate and lanthanum.

M Korc, M H Schöni
PMCID: PMC304411  PMID: 3469669

Abstract

The effects of extracellular phosphate and lanthanum on cytosolic free Ca2+ [( Ca2+]i) levels were studied in isolated rat pancreatic acini. In the presence of 1.28 mM Ca2+ and 1.0 mM phosphate, the mean resting [Ca2+]i level was 120 nM. Omission of phosphate from incubation medium significantly lowered this value to 94 nM. The gastrointestinal hormone cholecystokinin octapeptide (CCK-8) rapidly enhanced both [Ca2+]i levels and 45Ca2+ efflux, irrespective of the presence or absence of phosphate. Lanthanum (0.1 mM), a compound known to block transmembrane Ca2+ fluxes, attenuated both actions of CCK-8, but only in the absence of extracellular phosphate. There was a concomitant decrease in amylase secretion induced by 0.1 nM CCK-8 but not by 10 nM CCK-8, without a significant change in cellular ATP levels. The inhibitory actions of lanthanum on CCK-8-stimulated [Ca2+]i levels were very rapid and were mimicked only by prolonged incubation of acini in Ca2+-free medium supplemented with EGTA. Omission of phosphate from incubation medium also lowered basal [Ca2+]i levels in IM-9 lymphocytes. These findings suggest that extracellular phosphate may modulate resting [Ca2+]i levels in pancreatic acini and other cell types and that mobilization of intracellular Ca2+ may partly depend on the availability of a lanthanum-sensitive pool of cell-surface Ca2+ that is not readily removed by EGTA.

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Selected References

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  1. Aubier M., Murciano D., Lecocguic Y., Viires N., Jacquens Y., Squara P., Pariente R. Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. N Engl J Med. 1985 Aug 15;313(7):420–424. doi: 10.1056/NEJM198508153130705. [DOI] [PubMed] [Google Scholar]
  2. Barlas N., Jensen R. T., Gardner J. D. Cholecystokinin-induced restricted stimulation of pancreatic enzyme secretion. Am J Physiol. 1982 May;242(5):G464–G469. doi: 10.1152/ajpgi.1982.242.5.G464. [DOI] [PubMed] [Google Scholar]
  3. Bieger W., Peter S., Völkl A., Kern H. F. Amino acid transport in the rat exocrine pancreas. II. Inhibition by lanthanum and tetracaine. Cell Tissue Res. 1977 May 10;180(1):45–62. doi: 10.1007/BF00227029. [DOI] [PubMed] [Google Scholar]
  4. Bieger W., Seybold J., Kern H. F. Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. III. Effect of cobalt, lanthanum and antimycin A. Virchows Arch A Pathol Anat Histol. 1975 Nov 28;368(4):329–345. doi: 10.1007/BF00432310. [DOI] [PubMed] [Google Scholar]
  5. Bruzzone R., Pozzan T., Wollheim C. B. Caerulein and carbamoylcholine stimulate pancreatic amylase release at resting cytosolic free Ca2+. Biochem J. 1986 Apr 1;235(1):139–143. doi: 10.1042/bj2350139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Burgess G. M., Godfrey P. P., McKinney J. S., Berridge M. J., Irvine R. F., Putney J. W., Jr The second messenger linking receptor activation to internal Ca release in liver. Nature. 1984 May 3;309(5963):63–66. doi: 10.1038/309063a0. [DOI] [PubMed] [Google Scholar]
  7. DeFronzo R. A., Lang R. Hypophosphatemia and glucose intolerance: evidence for tissue insensitivity to insulin. N Engl J Med. 1980 Nov 27;303(22):1259–1263. doi: 10.1056/NEJM198011273032203. [DOI] [PubMed] [Google Scholar]
  8. Dubyak G. R., De Young M. B. Intracellular Ca2+ mobilization activated by extracellular ATP in Ehrlich ascites tumor cells. J Biol Chem. 1985 Sep 5;260(19):10653–10661. [PubMed] [Google Scholar]
  9. Geras E., Rebecchi M. J., Gershengorn M. C. Evidence that stimulation of thyrotropin and prolactin secretion by thyrotropin-releasing hormone occur via different calcium-mediated mechanisms: studies with verapamil. Endocrinology. 1982 Mar;110(3):901–906. doi: 10.1210/endo-110-3-901. [DOI] [PubMed] [Google Scholar]
  10. Knochel J. P. The pathophysiology and clinical characteristics of severe hypophosphatemia. Arch Intern Med. 1977 Feb;137(2):203–220. [PubMed] [Google Scholar]
  11. Korc M., Bailey A. C., Williams J. A. Regulation of protein synthesis in normal and diabetic rat pancreas by cholecystokinin. Am J Physiol. 1981 Aug;241(2):G116–G121. doi: 10.1152/ajpgi.1981.241.2.G116. [DOI] [PubMed] [Google Scholar]
  12. Korc M. Effect of lanthanum on pancreatic protein synthesis in streptozotocin-diabetic rats. Am J Physiol. 1983 Mar;244(3):G321–G326. doi: 10.1152/ajpgi.1983.244.3.G321. [DOI] [PubMed] [Google Scholar]
  13. Korc M. Regulation of pancreatic protein synthesis by cholecystokinin and calcium. Am J Physiol. 1982 Jul;243(1):G69–G75. doi: 10.1152/ajpgi.1982.243.1.G69. [DOI] [PubMed] [Google Scholar]
  14. Korc M., Williams J. A., Goldfine I. D. Stimulation of the glucose transport system in isolated mouse pancreatic acini by cholecystokinin and analogues. J Biol Chem. 1979 Aug 25;254(16):7624–7629. [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Langer G. A., Frank J. S. Lanthanum in heart cell culture. Effect on calcium exchange correlated with its localization. J Cell Biol. 1972 Sep;54(3):441–455. doi: 10.1083/jcb.54.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. O'Connor L. R., Wheeler W. S., Bethune J. E. Effect of hypophosphatemia on myocardial performance in man. N Engl J Med. 1977 Oct 27;297(17):901–903. doi: 10.1056/NEJM197710272971702. [DOI] [PubMed] [Google Scholar]
  18. Ochs D. L., Korenbrot J. I., Williams J. A. Intracellular free calcium concentrations in isolated pancreatic acini; effects of secretagogues. Biochem Biophys Res Commun. 1983 Nov 30;117(1):122–128. doi: 10.1016/0006-291x(83)91549-8. [DOI] [PubMed] [Google Scholar]
  19. Pandol S. J., Schoeffield M. S., Sachs G., Muallem S. Role of free cytosolic calcium in secretagogue-stimulated amylase release from dispersed acini from guinea pig pancreas. J Biol Chem. 1985 Aug 25;260(18):10081–10086. [PubMed] [Google Scholar]
  20. Rampini C., Dubois C., Barbu V. Phosphate depletion decrease mitogen-mediated stimulation of phospholipid synthesis in human peripheral lymphocytes. Biochem Biophys Res Commun. 1984 Jan 13;118(1):371–377. doi: 10.1016/0006-291x(84)91111-2. [DOI] [PubMed] [Google Scholar]
  21. Scheele G., Haymovits A. Cholinergic and peptide-stimulated discharge of secretory protein in guinea pig pancreatic lobules. Role of intracellular and extracellular calcium. J Biol Chem. 1979 Oct 25;254(20):10346–10353. [PubMed] [Google Scholar]
  22. Tsien R. Y., Pozzan T., Rink T. J. Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J Cell Biol. 1982 Aug;94(2):325–334. doi: 10.1083/jcb.94.2.325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Wakasugi H., Stolze H., Haase W., Schulz I. Effect of La3+ on secretagogue-induced Ca2+ fluxes in rat isolated pancreatic acinar cells. Am J Physiol. 1981 Apr;240(4):G281–G289. doi: 10.1152/ajpgi.1981.240.4.G281. [DOI] [PubMed] [Google Scholar]

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