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Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine

Cell and Tissue Research volume 269, pages 213–220 (1992)Cite this article

Summary

Paneth cells located at the bottom of intestinal crypts may play a role in controlling the bacterial milieu of the intestine. Using morphometry to clarify the secretory mechanism of the Paneth cells, we studied the ultrastructural changes in mouse Paneth cells produced following intra-arterial perfusion with Hanks' balanced salt solution containing a cholinergic muscarinic secretagogue (bethanechol), a neuroblocking agent (tetrodotoxin), or a G-protein activator (NAF/AlCl3). Bethanechol (2×10-4 mol/l) induced Paneth-cell secretion. Many Paneth cells massively exocytosed their secretory material into the crypt lumen; the enhanced secretion caused degranulation and vacuole formation. However, tetrodotoxin (2×10-6 mol/l) did not prevent the bethanechol-enhanced secretion by the Paneth cells. NaF (1×10-2 mol/l) and AlCl3 (1×10-5 mol/l) induced massive exocytosis of the Paneth cells; the exocytotic figures were similar to those observed in mice stimulated by bethanechol. G-protein activation was followed by a sequence of intracellular events, resulting in exocytosis.

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References

  • Ahonen A, Penttilä A (1975) Effects of fasting and feeding and pilocarpine on Paneth cells of the mouse. Scand J Gastroenterol 10:347–352

    Google Scholar 

  • Balas D, Senegas F, Frexinos J, Pradayrol L, Broussy J, Ribet A (1974) Action des hormones digestives sur la muqueuse jéjunale et iléale chez la souris et le hamster. Étude histophysiologique. Biol Gastroenterol 7:187–199

    Google Scholar 

  • Basbaum CB, Ueki I, Brezina L, Nadel JA (1981) Tracheal submucosal gland serous cells stimulated in vitro with adrenergic and cholinergic agonists: a morphometric study. Cell Tissue Res 220:481–498

    Google Scholar 

  • Batzri S, Amsterdam A, Selinger Z, Ohad I, Schramm M (1971) Epinephrine-induced vacuole formation in parotid gland cells and its independence of the secretory process. Proc Natl Acad Sci USA 68:121–123

    Google Scholar 

  • Bigay J, Deterre P, Pfister C, Chabre M (1985) Fluoroaluminates activate transducin-GDP by mimicking the γ-phosphate of GTP in its binding site. FEBS Lett 191:181–185

    Google Scholar 

  • Birnbaumer L, Abramowitz J, Brown AM (1990) Receptor-effector coupling by G proteins. Biochim Biophys Acta 1031:163–224

    Google Scholar 

  • Brom C, Brom J, König W (1991) G protein activation and mediator release from human neutrophils and platelets after stimulation with sodium fluoride and receptor-mediated stimuli. Immunology 73:287–292

    Google Scholar 

  • Chung LP, Keshav S, Gordon S (1988) Cloning the human lysozyme cDNA: inverted Alu repeat in the mRNA and in situ hybridization for macrophages and Paneth cells. Proc Natl Acad Sci USA 85:6227–6231

    Google Scholar 

  • Cordier R (1923) Contribution à l'étude de la cellule de Ciaccio-Masson et de la cellule de Paneth. C R Soc Biol (Paris) 88:1227–1230

    Google Scholar 

  • Elferink JGR, Alsbach EJJ, Riemersma JC (1980) The interaction of fluoride with rabbit polymorphonuclear leukocytes: induction of exocytosis and cytolysis. Biochem Pharmacol 29:3051–3057

    Google Scholar 

  • Erlandsen SL, Chase DG (1972a) Paneth cell function: phagocytosis and intracellular digestion of intestinal microorganisms. I. Hexamita muris. J Ultrastruct Res 41:296–318

    Google Scholar 

  • Erlandsen SL, Chase DG (1972b) Paneth cell function: phagocytosis and intracellular digestion of intestinal microorganisms. II. Spiral microorganism. J Ultrastruct Res 41:319–333

    Google Scholar 

  • Erlandsen SL, Parsons JA, Taylor TD (1974) Ultrastructural immunocytochemical localization of lysozyme in the Paneth cells of man. J Histochem Cytochem 22:401–413

    Google Scholar 

  • Erlandsen SL, Rodning CB, Montero C, Parsons JA, Lewis EA, Wilson ID (1976) Immunocytochemical identification and localization of immunoglobulin A within Paneth cells of the rat small intestine. J Histochem Cytochem 24:1085–1092

    Google Scholar 

  • Furness JB, Costa M (1987) The enteric nervous system. Churchill Livingstone, Edinburgh London Melbourne

    Google Scholar 

  • Gomperts BD (1990) GE: a GTP-binding protein mediating exocytosis. Annu Rev Physiol 52:591–606

    Google Scholar 

  • Habara Y, Satoh Y, Saito T, Kanno T (1990) A G-protein activator, NaF, induces [Ca2+]o-dependent [Ca2+]c oscillation and secretory response in rat pancreatic acini. Biomed Res 11:389–398

    Google Scholar 

  • Hally AD (1958) The fine structure of the Paneth cell. J Anat 92:268–277

    Google Scholar 

  • Hughes BP, Barritt GJ (1987) The stimulation by sodium fluoride of plasma-membrane Ca2+ inflow in isolated hepatocytes. Evidence that a GTP-binding regulatory protein is involved in the hormonal stimulation of Ca2+ inflow. Biochem J 245:41–47

    Google Scholar 

  • Kanno T, Matsumoto T, Mori M, Oyamada M, Nevalainen TJ (1984) Secretion prevents hyporeactive and morphological responses of rat pancreatic acinar cells to stimulation with supraoptimal concentration of cholecystokinin-octapeptide. Biomed Res 5:355–370

    Google Scholar 

  • Klockars M (1974) Concentration and immunohistochemical localization of lysozyme in germ-free and conventionally reared rats. Acta Pathol Microbiol Scand [A] 82:675–682

    Google Scholar 

  • Knight DE, Grafenstein H, Athayde CM (1989) Calcium-dependent and calcium-independent exocytosis. Trend Neurosci 12:451–458

    Google Scholar 

  • Kraal B, Graaf JM de, Mesters JR, Hoof PJM van, Jacquet E, Parmeggiani A (1990) Fluoroalminates do not affect the guanine-nucleotide binding centre of the peptide chain elongation factor EF-Tu. Eur J Biochem 192:305–309

    Google Scholar 

  • Kurosumi K, Shibuichi I, Tosaka H (1981) Ultrastructural studies on the secretory mechanism of goblet cells in the rat jejunal epithelium. Arch Histol Jpn 44:263–284

    Google Scholar 

  • Masty J, Stradley RP (1991) Paneth cell degranulation and lysozyme secretion during acute equine alimentary laminitis. Histochemistry 95:529–533

    Google Scholar 

  • Matozaki T, Sakamoto C, Nagao M, Nishizaki H, Baba S (1988) G protein in stimulation of PI hydrolysis by CCK in isolated rat pancreatic acinar cells. Am J Physiol 255:E652-E659

    Google Scholar 

  • McNabb PC, Tomasi TB (1981) Host defense mechanisms at mucosal surfaces. Annu Rev Microbiol 35:477–496

    Google Scholar 

  • Mertz LM, Horn VJ, Baum BJ, Ambudkar IS (1990) Calcium entry in rat parotid acini: activation by carbachol and aluminium fluoride. Am J Physiol 258:C654-C661

    Google Scholar 

  • Mürer EH, Davenport K, Siojo E, Day HJ (1981) Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets. Biochem J 194:187–192

    Google Scholar 

  • Neutra MR, O'Malley LJ, Specian RD (1982) Regulation of intestinal goblet cell secretion. II. A survey of potential secretagogues. Am J Physiol 242:G380-G387

    Google Scholar 

  • Olson RE, Erlandsen SL (1981) Paneth cell function: the effects of cholinergic and adrenergic drugs on lysozyme secretion. Anat Rec 199:186A

    Google Scholar 

  • Otto HF (1974) Die intestinale Paneth-Zelle. Fischer, Stuttgart

  • Otto HF, Lewerenz I (1973) Untersuchungen zur Ultrastruktur des Dünndarms keimfrei aufgezogener FW 49-Ratten 1. Epitheliale Befunde unter besonderer Berücksichtigung der Paneth-Zellen. Virchows Arch [A] 360:235–251

    Google Scholar 

  • Ouellette AJ, Greco RM, James M, Frederick D, Naftilan J, Fallon JT (1989) Developmental regulation of cryptdin, a corticostatin/defensin precursor mRNA in mouse small intestinal crypt epithelium. J Cell Biol 108:1687–1695

    Google Scholar 

  • Paneth J (1888) Über die secernierenden Zellen des Dünndarmepithels. Arch Mikrosk Anat 31:113–191

    Google Scholar 

  • Ritchie JM, Green NM (1985) Local anesthetics. In: Gilman AG, Goodman LS, Rall TW, Murad F (eds) Goodman and Gilman's the pharmacological basis of therapeutics, 7th edn. Macmillan, New York, pp 302–321

    Google Scholar 

  • Rodning CB, Wilson ID, Erlandsen SL (1976) Immunoglobulins within human small intestinal Paneth cells. Lancet I:984–987

    Google Scholar 

  • Rodning CB, Erlandsen SL, Wilson ID, Carpenter A-M (1982) Light microscopic morphometric analysis of rat ileal mucosa. II. Component quantitation of Paneth cells. Anat Rec 204:33–38

    Google Scholar 

  • Saito H, Kasajima T, Masuda A, Imai Y, Ishikawa M (1988) Lysozyme localization in human gastric and duodenal epithelium. An immunocytochemicla study. Cell Tissue Res 251:307–313

    Google Scholar 

  • Satoh Y (1984) Ultrastructure of Paneth cells in germ-free rats, with special reference to the secretory granules and lysosomes. Arch Histol Jpn 47:293–301

    Google Scholar 

  • Satoh Y (1988a) Effect of live and heat-killed bacteria on the secretory activity of Paneth cells in germ-free mice. Cell Tissue Res 251:87–93

    Google Scholar 

  • Satoh Y (1988b) Atropine inhibits the degranulation of Paneth cells in ex-germ-free mice. Cell Tissue Res 253:397–402

    Google Scholar 

  • Satoh Y, Vollrath L (1986) Quantitative electron microscopic observations on Paneth cells of germfree and ex-germfree Wistar rats. Anat Embryol (Berl) 173:317–322

    Google Scholar 

  • Satoh Y, Ishikawa K, Ono K, Vollrath L (1986a) Quantitative light microscopic observations on Paneth cells of germfree and ex-germfree Wistar rats. Digestion 34:115–121

    Google Scholar 

  • Satoh Y, Ishikawa K, Tanaka H, Ono K (1986b) Immunohistochemical observations of immunoglobulin A in the Paneth cells of germ-free and formely-germ-free rats. Histochemistry 85:197–201

    Google Scholar 

  • Satoh Y, Ishikawa K, Tanaka H, Oomori Y, Ono K (1988) Immunohistochemical observations of lysozyme in the Paneth cells of specific-pathogen-free and germ-free mice. Acta Histochem (Jena) 83:185–188

    Google Scholar 

  • Satoh Y, Ishikawa K, Oomori Y, Yamano Y, Ono K (1989) Effects of cholecystokinin and carbamylcholine on Paneth cell secretion in mice: a comparison with pancreatic acinar cells. Anat Rec 225:124–132

    Google Scholar 

  • Satoh Y, Ishikawa K, Oomori Y, Ono K (1991) Effect of sodium fluoride on Paneth cells, goblet cells, and exocrine pancreatic acinar cells in mice (abstract). Acta Anat Nippon 66:368

    Google Scholar 

  • Scheele G, Adler G, Kern H (1987) Exocytosis occurs at the lateral plasma membrane of the pancreatic acinar cell during supramaximal segretagogue stimulation. Gastroenterology 92:345–353

    Google Scholar 

  • Schwalbe G (1872) Beiträge zur Kenntnis der Drüsen in den Darmwandungen, insbesondere der Brunner'schen, Drüsen. Arch Mikrosk Anat 8:92–140

    Google Scholar 

  • Senegas-Balas F, Balas D, Pradayrol L, Laval J, Ribet A (1979) Comparative effects of CCK-PZ on certain intestinal hydrolases in the mucosa and in the luminal content of hamster jejunoileum. Acta Hepato-gastroenterol 26:486–492

    Google Scholar 

  • Shuttleworth TJ (1990) Fluoroalminate activation of different components of the calcium signal in an exocrine cell. Biochem J 269:417–422

    Google Scholar 

  • Sorimachi M, Nishimura S, Yamagami K, Yada T (1990) Histamine release by calcium from fluoride-activated rat mast cells: possible involvement of CaF2 formation. Med J Kagoshima Univ 42:11–21

    Google Scholar 

  • Specian RD, Neutra MR (1982) Regulation of intestinal goblet cell secretion. I. Role of parasympathetic stimulation. Am J Physiol 242:G370-G379

    Google Scholar 

  • Speece AJ (1964) Histochemical distribution of lysozyme activity in organs of normal mice and radiation chimeras. J Histochem Cytochem 12:384–391

    Google Scholar 

  • Stadel JM, Crooke ST (1989) Fluoride interaction with G-proteins. Biochem J 258:932–933

    Google Scholar 

  • Staley MW, Trier JS (1965) Morphologic heterogeneity of mouse Paneth cell granules before and after secretory stimulation. Am J Anat 117:365–384

    Google Scholar 

  • Sternweis PC, Gilman AG (1982) Aluminium: a requirement for activation of the regulatory component of adenylate cyclase by fluoride. Proc Natl Acad Sci USA 79:4888–4891

    Google Scholar 

  • Tojyo Y, Tanimura A, Matsui S, Matsumoto Y, Sugija H, Furuyama S (1991) NaF-induced amylase release from rat parotid cells is mediated by PI breakdown leading to Ca2+ mobilization. Am J Physiol 260:C194-C200

    Google Scholar 

  • Watanabe O, Baccino FM, Steer ML, Meldolesi J (1984) Supraximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. Am J Physiol 246:G457-G467

    Google Scholar 

  • Zeng YY, Benishin CG, Pang PKT (1989), Guanine nucleotide binding proteins may modulate gating of calcium channels in vascular smooth muscle. I. Studies with fluoride. J Pharmacol Exp Ther 250:343–351

    Google Scholar 

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Affiliations

  1. Department of Anatomy, Asahikawa, Medical College, Nishikagura 4-5, 078, Asahikawa, Japan

    Y. Satoh, K. Ishikawa, Y. Oomori, S. Takeda & K. Ono

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  1. Y. Satoh
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  2. K. Ishikawa
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  3. Y. Oomori
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  4. S. Takeda
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  5. K. Ono
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Satoh, Y., Ishikawa, K., Oomori, Y. et al. Bethanechol and a G-protein activator, NaF/AlCl3, induce secretory response in Paneth cells of mouse intestine. Cell Tissue Res 269, 213–220 (1992). https://doi.org/10.1007/BF00319611

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  • DOI: https://doi.org/10.1007/BF00319611

Key words

  • Paneth cells
  • Ultrastructure
  • Morphometry
  • Bethanechol
  • Fluoride ion
  • G-protein
  • Mouse (Balb/c)