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PMID: 15240573 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Extracellular calcium acts as a "third messenger" to regulate enzyme and alkaline secretion.

The Journal of cell biology ·Vol. 166 ·No. 1 ·2004-07-05 ·Pages 111-9

Caroppo R, Gerbino A, Fistetto G, Colella M, Debellis L, Hofer AM, Curci S

Abstract

It is generally assumed that the functional consequences of stimulation with Ca2+ -mobilizing agonists are derived exclusively from the second messenger action of intracellular Ca2+, acting on targets inside the cells. However, during Ca2+ signaling events, Ca2+ moves in and out of the cell, causing changes not only in intracellular Ca2+, but also in local extracellular Ca2+. The fact that numerous cell types possess an extracellular Ca2+ "sensor" raises the question of whether these dynamic changes in external [Ca2+] may serve some sort of messenger function. We found that in intact gastric mucosa, the changes in extracellular [Ca2+] secondary to carbachol-induced increases in intracellular [Ca2+] were sufficient and necessary to elicit alkaline secretion and pepsinogen secretion, independent of intracellular [Ca2+] changes. These findings suggest that extracellular Ca2+ can act as a "third messenger" via Ca2+ sensor(s) to regulate specific subsets of tissue function previously assumed to be under the direct control of intracellular Ca2+.

MeSH Terms
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology Adenine/analogs & derivatives,pharmacology Animals Calcium/metabolism Carbachol/pharmacology Electrodes Electrophysiology Enzyme Inhibitors/pharmacology Gastric Mucosa/metabolism,pathology Hydrogen-Ion Concentration Microscopy, Fluorescence Pepsinogen A/chemistry,metabolism Ranidae Signal Transduction Spermine/metabolism
Chemicals
Enzyme Inhibitors 9-(tetrahydro-2-furyl)-adenine Spermine Carbachol Pepsinogen A Adenine 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid Calcium
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Caroppo Rosa
Dipartimento di Fisiologia Generale ed Ambientale, Università di Bari, Italy.
Gerbino Andrea
Fistetto Gregorio
Colella Matilde
Debellis Lucantonio
Hofer Aldebaran M
Curci Silvana
References (65)
65 references, click to expand
  1. Extracellular calcium sensing and signalling.
    Nat Rev Mol Cell Biol. 2003 Jul;4(7):530-8 PMID: 12838336
  2. Na-H and Cl-HCO3 exchange in rabbit oxyntic cells using fluorescence microscopy.
    Am J Physiol. 1987 Jul;253(1 Pt 1):C30-6 PMID: 3037913
  3. Divalent cations suppress 3',5'-adenosine monophosphate accumulation by stimulating a pertussis toxin-sensitive guanine nucleotide-binding protein in cultured bovine parathyroid cells.
    Endocrinology. 1989 Jan;124(1):233-9 PMID: 2462488
  4. Acid secretagogues induce Ca2+ mobilization coupled to K+ conductance activation in rat parietal cells in tissue culture.
    Biochim Biophys Acta. 1989 Aug 15;1012(3):254-60 PMID: 2758038
  5. Effect of histamine on the basolateral K+ conductance of frog stomach oxyntic cells and surface epithelial cells.
    Am J Physiol. 1990 Apr;258(4 Pt 1):G631-6 PMID: 2333976
  6. An adenosine triphosphatase from frog gastric mucosa.
    Biochim Biophys Acta. 1965 Sep 20;105(3):472-82 PMID: 4222036
  7. The control of pepsinogen secretion.
    Ann N Y Acad Sci. 1967 Jan 26;140(2):709-23 PMID: 4961720
  8. The effect of inhibitors of HCl secretion on the unidirectional fluxes of chloride across bullfrog gastric mucosa.
    Biochim Biophys Acta. 1968 Jan 3;150(1):136-45 PMID: 5642627
  9. Transport of calcium in the perfused submandibular gland of the cat.
    J Physiol. 1972 Jun;223(3):685-97 PMID: 5045737
  10. Acid-base balance in amphibian gastric mucosa.
    Am J Physiol. 1975 Sep;229(3):721-30 PMID: 2015
  11. Ultrastructural changes and cyclic AMP in frog oxyntic cells.
    J Cell Biol. 1978 Jan;76(1):31-42 PMID: 201646
  12. Quantitative ultrastructural studies on rat gastric zymogen cells under different physiological and experimental conditions.
    Cell Tissue Res. 1978 May 29;189(2):287-303 PMID: 657245
  13. Inhibition of adenylate cyclase in human blood platelets by 9-substituted adenine derivatives.
    J Cyclic Nucleotide Res. 1979;5(2):125-34 PMID: 221552
  14. Na+-dependent H+ and Cl- transport in in vitro frog gastric mucosa.
    Am J Physiol. 1980 May;238(5):G403-13 PMID: 6966473
  15. Lack of interaction between acid and pepsinogen secretion in isolated gastric glands.
    Am J Physiol. 1983 Dec;245(6):G775-9 PMID: 6318567
  16. Transsarcolemmal calcium movements in arterially perfused rabbit right ventricle measured with extracellular calcium-sensitive dyes.
    Circ Res. 1984 Apr;54(4):461-7 PMID: 6325038
  17. Regulation of intracellular pH in the stomach.
    Annu Rev Physiol. 1987;49:19-33 PMID: 3551797
  18. Cytosolic Ca2+ gradients triggering unidirectional fluid secretion from exocrine pancreas.
    Nature. 1990 Dec 20-27;348(6303):735-8 PMID: 1701852
  19. Capacitative calcium entry revisited.
    Cell Calcium. 1990 Nov-Dec;11(10):611-24 PMID: 1965707
  20. Diversity of K+ channels in the basolateral membrane of resting Necturus oxyntic cells.
    J Membr Biol. 1991 Sep;123(3):209-21 PMID: 1744900
  21. Gastric chief cells: receptors and signal-transduction mechanisms.
    Gastroenterology. 1992 Feb;102(2):699-710 PMID: 1310085
  22. Acetylcholine-evoked increase in the cytoplasmic Ca2+ concentration and Ca2+ extrusion measured simultaneously in single mouse pancreatic acinar cells.
    J Biol Chem. 1992 Feb 25;267(6):3569-72 PMID: 1310974
  23. Spatial and temporal distribution of agonist-evoked cytoplasmic Ca2+ signals in exocrine acinar cells analysed by digital image microscopy.
    EMBO J. 1992 Apr;11(4):1623-9 PMID: 1563357
  24. Calcium signalling and the triggering of secretion in adrenal chromaffin cells.
    Pharmacol Ther. 1991 Nov;52(2):173-89 PMID: 1818335
  25. Microelectrode determination of oxyntic cell pH in intact frog gastric mucosa. Effect of histamine.
    Pflugers Arch. 1992 Dec;422(3):253-9 PMID: 1488284
  26. Nonparallel secretion of pepsinogen and acid by gastric oxyntopeptic cells of the toad (Bufo marinus).
    Am J Physiol. 1993 Nov;265(5 Pt 1):G934-41 PMID: 8238523
  27. Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.
    Nature. 1993 Dec 9;366(6455):575-80 PMID: 8255296
  28. Calcium and hormone action.
    Annu Rev Physiol. 1994;56:297-319 PMID: 8010742
  29. Model of bicarbonate secretion by resting frog stomach fundus mucosa. I. Transepithelial measurements.
    Pflugers Arch. 1994 Oct;428(5-6):648-54 PMID: 7838688
  30. Model of bicarbonate secretion by resting frog stomach fundus mucosa. II. Role of the oxyntopeptic cells.
    Pflugers Arch. 1994 Oct;428(5-6):655-63 PMID: 7838689
  31. A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit.
    Biochimie. 1995;77(5):333-40 PMID: 8527486
  32. Localization of Ca2+ extrusion sites in pancreatic acinar cells.
    J Biol Chem. 1996 Mar 29;271(13):7615-9 PMID: 8631796
  33. Variant AE2 anion exchanger transcripts accumulate in multiple cell types in the chicken gastric epithelium.
    J Biol Chem. 1996 Apr 12;271(15):8895-902 PMID: 8621532
  34. Ca2+ influx and activation of a cation current are coupled to intracellular Ca2+ release in peptidergic neurons of Aplysia californica.
    J Physiol. 1996 Aug 1;494 ( Pt 3):627-39 PMID: 8865062
  35. Immunocytochemical localization of polyamines in the gastrointestinal tracts of rats and mice.
    Histochem Cell Biol. 1996 Nov;106(5):465-71 PMID: 8950604
  36. Is resting state HCO3- secretion in frog gastric fundus mucosa mediated by apical Cl(-)-HCO3- exchange?
    J Physiol. 1997 Mar 15;499 ( Pt 3):763-71 PMID: 9130171
  37. Polarized expression of Ca2+ pumps in pancreatic and salivary gland cells. Role in initiation and propagation of [Ca2+]i waves.
    J Biol Chem. 1997 Jun 20;272(25):15771-6 PMID: 9188473
  38. Distribution of Ca2+ extrusion sites on the mouse pancreatic acinar cell surface.
    Cell Calcium. 1997 Jul;22(1):5-10 PMID: 9232347
  39. Capacitative Ca2+ entry (CCE) induced by luminal and basolateral ATP in polarised MDCK-C7 cells is restricted to the basolateral membrane.
    Cell Calcium. 1997 Aug;22(2):121-8 PMID: 9292230
  40. The Ca2+-sensing receptor: a target for polyamines.
    Am J Physiol. 1997 Oct;273(4 Pt 1):C1315-23 PMID: 9357776
  41. Plasma membrane Ca2+-ATPase extrudes Ca2+ from hair cell stereocilia.
    J Neurosci. 1998 Jan 15;18(2):610-24 PMID: 9425003
  42. Free [Ca2+] dynamics measured in agonist-sensitive stores of single living intact cells: a new look at the refilling process.
    EMBO J. 1998 Apr 1;17(7):1986-95 PMID: 9524121
  43. Alkaline secretion by frog gastric glands measured with pH microelectrodes in the gland lumen.
    J Physiol. 1998 Nov 15;513 ( Pt 1):235-41 PMID: 9782173
  44. Interstitial Ca2+ undergoes dynamic changes sufficient to stimulate nerve-dependent Ca2+-induced relaxation.
    Am J Physiol. 1999 Mar;276(3 Pt 2):H1035-42 PMID: 10070089
  45. The Ca2+-sensing receptor in the rabbit cortical thick ascending limb (CTAL) is functionally not coupled to phospholipase C.
    Pflugers Arch. 1999 Apr;437(5):716-23 PMID: 10087149
  46. Transmembrane regulation of intracellular calcium by a plasma membrane sodium/calcium exchanger in mouse ova.
    Biol Reprod. 1999 May;60(5):1137-43 PMID: 10208975
  47. Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas.
    J Biol Chem. 1999 Jul 16;274(29):20561-8 PMID: 10400686
  48. Dynamic regulation of [Ca2+]i by plasma membrane Ca(2+)-ATPase and Na+/Ca2+ exchange during capacitative Ca2+ entry in bovine vascular endothelial cells.
    Cell Calcium. 1999 May;25(5):333-43 PMID: 10463097
  49. Regulation of exocytosis via release of Ca(2+) from intracellular stores.
    Bioessays. 1999 Oct;21(10):861-5 PMID: 10497336
  50. Basolateral store-operated Ca(2+)-entry in polarized human bronchial and colonic epithelial cells.
    Cell Calcium. 1999 Dec;26(6):253-60 PMID: 10668563
  51. Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation.
    J Cell Biol. 2000 Mar 6;148(5):1063-74 PMID: 10704454
  52. Renal interstitial Ca(2+).
    Am J Physiol Renal Physiol. 2000 Apr;278(4):F644-9 PMID: 10751226
  53. L-amino acid sensing by the extracellular Ca2+-sensing receptor.
    Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4814-9 PMID: 10781086
  54. Intracellular Ca2+ and Cl- channel activation in secretory cells.
    Annu Rev Physiol. 2000;62:493-513 PMID: 10845100
  55. Intercellular communication mediated by the extracellular calcium-sensing receptor.
    Nat Cell Biol. 2000 Jul;2(7):392-8 PMID: 10878803
  56. Expression and function of Na+HCO3- cotransporters in the gastrointestinal tract.
    Ann N Y Acad Sci. 2000;915:1-14 PMID: 11193561
  57. Extracellular calcium sensing and extracellular calcium signaling.
    Physiol Rev. 2001 Jan;81(1):239-297 PMID: 11152759
  58. Gastroduodenal mucosal alkaline secretion and mucosal protection.
    News Physiol Sci. 2001 Feb;16:23-8 PMID: 11390942
  59. Asymmetrical, agonist-induced fluctuations in local extracellular [Ca(2+)] in intact polarized epithelia.
    EMBO J. 2001 Nov 15;20(22):6316-26 PMID: 11707403
  60. Bradykinin and ATP accelerate Ca(2+) efflux from rat sensory neurons via protein kinase C and the plasma membrane Ca(2+) pump isoform 4.
    Neuron. 2002 Jan 3;33(1):113-22 PMID: 11779484
  61. Polarized calcium and calmodulin signaling in secretory epithelia.
    Physiol Rev. 2002 Jul;82(3):701-34 PMID: 12087133
  62. The effects of HCl and CaCl(2) injections on intracellular calcium and pH in voltage-clamped snail (Helix aspersa) neurons.
    J Gen Physiol. 2002 Oct;120(4):567-79 PMID: 12356857
  63. Alternative splicing and interaction with di- and polyvalent cations control the dynamic range of acid-sensing ion channel 1 (ASIC1).
    J Biol Chem. 2002 Nov 1;277(44):41597-603 PMID: 12198124
  64. Evidence that Ca(2+) cycling by the plasma membrane Ca(2+)-ATPase increases the 'excitability' of the extracellular Ca(2+)-sensing receptor.
    J Cell Sci. 2003 Apr 15;116(Pt 8):1527-38 PMID: 12640037
  65. Calcium signalling: dynamics, homeostasis and remodelling.
    Nat Rev Mol Cell Biol. 2003 Jul;4(7):517-29 PMID: 12838335
Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200310145
Published
2004-07-05
Pages
111-9
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172151
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200310145 PMC Full Text View journal details
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