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Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

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Summary

A human intestinal epithelial cell line (Intestine 407) is known to retain receptors for intestinal secretagogues such as acetylcholine (ACh), histamine, serotonin (5-HT) and vasoactive intestinal peptide (VIP). The cells were also found to possess separate receptors for secretin and ATP, the stimulation of which elicited transient hyperpolarizations coupled to decreased membrane resistances. These responses were reversed in polarity at the K+ equilibrium potential. The hyperpolarizing responses to six agonists were reversibly inhibited by quinine or quinidine. By means of Ca2+-selective microelectrodes, increases in the cytosolic free Ca2+ concentration were observed in response to individual secretagogues. The time course of Ca2+ responses coincided with that of hyperpolarizing responses. The responses to ACh and 5-HT were abolished by a reduction in the extracellular Ca2+ concentration down to pCa 7 or by application of Co2+. Thus, in Intestine 407 cells, not only the intestinal secretagogues, which are believed to act via increased cytosolic Ca2+ (ACh, 5-HT and histamine), but also those which elevate cyclic AMP (VIP, secretin and ATP) induce increases in cytosolic Ca2+, thereby activating the K+ conductance. It is likely that the origin of increased cytosolic Ca2+ is mainly extracellular for ACh- and 5-HT-induced responses, whereas histamine, VIP, secretin and ATP mobilize Ca2+ from the internal compartment.

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References

  • Armstrong, C.M. 1971. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons.J. Gen. Physiol. 55:413–437

    Google Scholar 

  • Baker, P.F., Meves, H., Ridgway, E.B. 1973. Effects of manganese and other agents on the calcium uptake that follows depolarization of squid axons.J. Physiol. (LOndon) 231:511–526

    Google Scholar 

  • Binder, H.J., Lemp, G.F., Gardner, J.D. 1980. Receptors for vasoactive intestinal peptide and secretin on small intestinal epithelial cells.Am. J. Physiol. 238:G190-G196

    PubMed  Google Scholar 

  • Bolton, J.E., Field, M. 1977. Ca ionophore-stimulated ion secretion in rabbit ileal mucosa: Relation to actions of cyclic 3′,5′-AMP and carbamylcholine.J. Membrane Biol. 35:159–174

    Google Scholar 

  • Cartwright, C.A., McRoberts, J.A., Mandel, K.G., Dharmsathaphorn, K. 1985. Synergistic action of cyclic adenosine monophosphate- and calcium-mediated chloride secretion in a colonic epithelial cell line.J. Clin. Invest. 76:1837–1842

    PubMed  Google Scholar 

  • Chang, E.B., Brown, D.R., Wang, N.S., Field, M. 1986. Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa.J. Clin. Invest. 78:281–287

    PubMed  Google Scholar 

  • Cooke, H.J. 1987. Neural and humoral regulation of small intestinal electrolyte transport.In: Physiology of Gastrointestinal Tract. L.R. Johnson, editor. pp. 1307–1350. Raven, New York

    Google Scholar 

  • DeRiemer, S.A., Strong, J.A., Albert, K.A., Greengard, P., Kaczmarek, L.K. 1985. Enhancement of calcium current inAplysia neurones by phorbol ester and protein kinase C.Nature (London) 313:313–316

    Google Scholar 

  • Dharmsathaphorn, K., Harms, V., Yamashiro, D.H., Hughes, R.J., Binder, H.J., Wright, E.M. 1983. Preferential binding of vasoactive intestinal polypeptide to basolateral membrane of rat and rabbit enterocytes.J. Clin. Invest. 71:27–35

    PubMed  Google Scholar 

  • Dharmsathaphorn, K., Pandol, S.J. 1986. Mechanism of chloride secretion induced by carbachol in a colonic epithelial cell line.J. Clin. Invest. 77:348–354

    PubMed  Google Scholar 

  • Donowitz, M. 1983. Ca2+ in the control of active Na and Cl transport: Involvement in neurohumoral action.Am. J. Physiol. 245:G165-G177

    Google Scholar 

  • Donowitz, M., Welsh, M.J. 1987. Regulation of mammalian small intestinal electrolyte secretion.In: Physiology of Gastrointestinal Tract. L.R. Johnson, editor. pp. 1351–1388 Raven, New York

    Google Scholar 

  • Endo, M. 1975. Mechanisms of action of caffeine on the sarcoplasmic reticulum of skeletal muscle.Proc. Jpn. Acad. 51:479–484

    Google Scholar 

  • Findlay, I., Dunne, M.J., Ullrich, S., Wollheim, C.B., Petersen, O.H. 1985. Quinine inhibits Ca2+-independent K+ channels whereas tetraethylammonium inhibits Ca2+-activated K+ channels in insulin-secreting cells.FEBS Lett. 185:4–8

    PubMed  Google Scholar 

  • Frizzell, R.A. 1977. Active chloride secretion by rabbit colon: Calcium dependent stimulation by ionophore A23187.J. Membrane Biol. 35:175–187

    Google Scholar 

  • Gaginella, T.S., Phillips, S.F., Dozois, R.R., Go, V.L.W. 1978. Stimulation of adenylate cyclase in homogenates of isolated intestinal epithelial cells from hamsters. Effects of gastrointestinal hormones, prostaglandins, and deoxycholic and ricinoleic acids.Gastroenterology 74:11–15

    PubMed  Google Scholar 

  • Hagiwara, S., Takahashi, K. 1967. Surface density of calcium ions and calcium spikes on the barnacle muscle fiber membrane.J. Gen. Physiol. 50:583–601

    PubMed  Google Scholar 

  • Hardcastle, J., Hardcastle, P.T. 1986. The involvement of basolateral potassium channels in the intestinal response to secretagogues in the rat.J. Physiol. (London) 379:331–345

    Google Scholar 

  • Hardcastle, J., Hardcastle, P.T. 1987. The secretory actions of histamine in rat small intestine.J. Physiol. (London) 388:521–532

    Google Scholar 

  • Hardcastle, J., Hardcastle, P.T., Redfern, J.S. 1981. Action of 5-hydroxytryptamine on intestinal ion transport in the rat.J. Physiol. (London) 320:41–55

    Google Scholar 

  • Hazama, A., Okada, Y. 1988. Ca2+ sensitivity of volume-regulatory K+ and Cl− channels in cultured human epithelial cells.J. Physiol. (London) 402:687–702

    Google Scholar 

  • Hazama, A., Yada, T., Okada, Y. 1985. HeLa cells have histamine H1-receptors which mediate activation of the K+ conductance.Biochim. Biophys. Acta 845:249–253

    Article  PubMed  Google Scholar 

  • Henle, G., Deinhardt, F. 1957. The establishment of strains of human cells in tissue culture.J. Immunol. 79:54–59

    PubMed  Google Scholar 

  • Hughes, J.M., Murad, F., Chang, B., Guerrant, R.L. 1978. Role of cyclic GMP in the action of heat-stable enterotoxin ofEscherichia coli.Nature (London) 271:755–756

    Google Scholar 

  • Ilundain, A., O'Brien, J.A., Burton, K.A., Sepulveda, F.V. 1987. Inositol trisphosphate and calcium mobilisation in permeabilised enterocytes.Biochim. Biophys. Acta 896:113–116

    PubMed  Google Scholar 

  • Itoh, A., Ueda, S., Okada, Y. 1989. Chloride current activation induced by intestinal secretagogues in an intestinal epithelial cell line.Jpn. J. Physiol. (Abstr.) (in press)

  • Juzu, H.A., Holdsworth, E.S. 1980. New evidence for the role of cyclic AMP in the release of mitochondrial calcium.J. Membrane Biol. 52:185–186

    Google Scholar 

  • Kelepouris, E., Agus, Z.S., Civan, M.M. 1985. Intracellular calcium activity in split frog skin epithelium: Effect of cAMP.J. Membrane Biol. 88:113–121

    Google Scholar 

  • Klaeveman, H.L., Conlon, T.P., Levy, A.G., Garoner, J.D. 1975. Effects of gastrointestinal hormones on adenylate cyclase activity in human jejunal mucosa.Gastroenterology 68:667–675

    PubMed  Google Scholar 

  • Korman, L.Y., Lemp, G.F., Jackson, M.J., Gardner, J.D. 1982. Mechanism of action of ATP on intestinal epithelial cells. Cyclic AMP-mediated stimulation of active ion transport.Biochim. Biophys. Acta 721:47–54

    PubMed  Google Scholar 

  • Kuno, M., Gardner, P. 1987. Ion channels activated by inositol 1,4,5-trisphosphate in plasma membrane of human T-lymphocytes.Nature (London) 326:301–304

    Google Scholar 

  • Laburthe, M., Mangeat, P., Marchis-Mouren, G., Rosselin, G. 1979a. Activation of cyclic AMP-dependent protein kinases by vasoactive intestinal peptide (VIP) in isolated intestinal epithelial cells from rat.Life Sci. 25:1931–1938

    PubMed  Google Scholar 

  • Laburthe, M., Prieto, J.C., Amiranoff, B., Dupont, C., Hui Bon Hoa, D., Rosselin, G. 1979b. Interaction of vasoactive intestinal peptide with isolated intestinal epithelial cells from rat. 2. Characterization and structural requirements of the stimulatory effect of vasoactive intestinal peptide on production of 3′:5′-monophosphate.Eur. J. Biochem. 96:239–248

    PubMed  Google Scholar 

  • Lee, C.O., Taylor, A., Windhager, E.E. 1980. Cytosolic calcium ion activity in epithelial cells ofNecturus, kidney.Nature (London) 287:859–861

    Google Scholar 

  • Mandel, K.G., McRoberts, J.A., Beuerlein, G., Foster, E.S., Dharmsathaphorn, K., 1986. Ba2+ inhibition of VIP- and A23187-stimulated Cl− secretion by T84 cell monolayer.Am. J. Physiol. 250:C486-C494

    PubMed  Google Scholar 

  • McRoberts, J.A., Beuerlein, G., Dharmsathaphorn, K. 1985. Cyclic AMP and Ca2+-activated K+ transport in a human colonic epithelial cell line.J. Biol. Chem. 260:14163–14172

    PubMed  Google Scholar 

  • Moore, L., Pastan, I. 1977. Energy-dependent calcium uptake activity in cultured mouse fibroblast microsomes. Regulation of the uptake system by cell density.J. Biol. Chem. 252:6304–6309

    PubMed  Google Scholar 

  • Morris, A.P., Gallacher, D.V., Lee, J.A.C. 1986. A large conductance, voltage- and calcium-activated K+ channel in the basolateral membrane of rat enterocytes.FEBS Lett. 206:87–92

    PubMed  Google Scholar 

  • Nishizuka, Y. 1984. The role of protein kinase C in cell surface signal transduction and tumour promotion.Nature (London) 308:693–698

    Google Scholar 

  • O'Doherty, J., Stark, R.J. 1981. Transmembrane and transepithelial movement of calcium during stimulus-secretion coupling.Am. J. Physiol. 241:G150-G158

    PubMed  Google Scholar 

  • O'Doherty, J., Stark, R.J., Crane, S.J., Brugge, K.L. 1983. Changes in cytosolic calcium during cholinergic and adrenergic stimulation of the parotid salivary gland.Pfluegers Arch. 398:241–246

    Google Scholar 

  • O'Doherty, J., Youmans, S.J., Armstrong, W.McD. 1980. Calcium regulation during stimulus-secretion coupling: Continuous measurement of intracellular calcium activities.Science 209:510–513

    PubMed  Google Scholar 

  • Oiki, S., Okada, Y. 1988. Clq induces chemotaxis and K+ conductance activation coupled to increased cytosolic Ca2+ in mouse fibroblasts.J. Immunol. 141:3177–3185

    PubMed  Google Scholar 

  • Okada, Y., Hazama, A., Yada, T. 1985. HeLa cells and Intestine 407 cell. Their differences in electrical membrane responses to secretagogues and in ecto-enzyme activities.Cell Struct. Funct. 10:515p (Abstr.)

    Google Scholar 

  • Osugi, T., Imaizumi, T., Mizushima, A., Uchida, S., Yoshida, H. 1986. 1-Oleoyl-2-acetyl-glycerol and phorbol diester stimulate Ca2+ influx through Ca2+ channels in neuroblastoma x glioma hybrid NG108-15 cells.Eur. J. Pharmacol. 126:47–51

    PubMed  Google Scholar 

  • Parker, I., Miledi, R. 1987. Inositol trisphosphate activates a voltage-dependent calcium influx inXenopus oocytes.Proc. R. Soc. London B 231:27–36

    Google Scholar 

  • Penner, R., Matthews, G., Neher, E. 1988. Regulation of calcium influx by second messengers in rat mast cells.Nature (London) 334:499–504

    Google Scholar 

  • Petersen, O.H. 1986. Potassium channels and fluid secretion.News Physiol. Sci. 1:92–95

    Google Scholar 

  • Schwartz, C.J., Kimberg, D.V., Sheerin, H.E., Field, M., Said, S.I. 1974. Vasoactive intestinal peptide stimulation of adenylate cyclase and active electrolyte secretion in intestinal mucosa.J. Clin. Invest. 54:536–544

    PubMed  Google Scholar 

  • Semrad, C.E., Chang, E.G. 1987. Calcium-mediated cyclic AMP inhibition of Na−H exchange in small intestine.Am. J. Physiol. 252:C315-C322

    PubMed  Google Scholar 

  • Sepulveda, F.V., Smith, S.M. 1987. Calcium transport by permeabilised rabbit small intestinal epithelial cells.Pfluegers Arch. 408:231–238

    Google Scholar 

  • Sheppard, D.N., Giraldez, F., Sepúlveda, F.V. 1988. Kinetics of voltage- and Ca2+ activation and Ba2+ blockade of a largeconductance K+ channel fromNecturus enterocytes.J. Membrane Biol. 105:65–75

    Google Scholar 

  • Sjölander, A. 1988. Direct effects of wheat germ agglutinin on inositol phosphate formation and cytosolic-free calcium level in Intestine 407 cells.J. Cell. Physiol. 134:473–478

    PubMed  Google Scholar 

  • Strong, J.A., Fox, A.P., Tsien, R.W., Kaczmarek, L.K. 1987. Stimulation of protein kinase C recruits convert calcium channels inAplysia bag cell neurons.Nature (London) 325:714–717

    Google Scholar 

  • Thomas, D.D., Knoop, F.C. 1983. Effect of heat-stable enterotoxin ofEscherichia coli on cultured mammalian cells.J. Infect. Dis. 147:450–459

    PubMed  Google Scholar 

  • Trimble, E.R., Burzzone, R., Biden, T.J., Farese, R.V. 1986. Secretin induces rapid increases in inositol triphosphate, cytosolic Ca2+ and diacylglycerol as well as cyclic AMP in rat pancreatic acini.Biochem. J. 239:257–261

    PubMed  Google Scholar 

  • Ueda, S., Loo, D.D.F., Sachs, G. 1987. Regulation of K+ channels in the basolateral membrane ofNecturus oxyntic cells.J. Membrane Biol. 97:31–41

    Google Scholar 

  • van Corven, E.J.J.M., Verbost, P.M., de Jong, M.D., van Os, C.H. 1987. Kinetics of ATP-dependent Ca2+ uptake by permeabilized rat enterocytes. Effects of inositol 1,4,5-trisphosphate.Cell Calcium 8:197–206

    PubMed  Google Scholar 

  • Velasco, G., Shears, S.B., Michell, R.H., Lazo, P.S. 1986. Calcium uptake by intracellular compartments in permeabilised enterocytes. Effect of inositol 1,4,5 trisphosphate.Biochem. Biophys. Res. Commun. 139:612–618

    PubMed  Google Scholar 

  • Vilven, J., Coronado, R. 1988. Opening of dihydropyridine calcium channels in skeletal muscle membranes by inositol trisphosphate.Nature (London) 336:587–589

    Google Scholar 

  • Wakelam, M.J.O., Murphy, G.J., Hruby, V.J., Houslay, M.D. 1986. Activation of two signal-transduction systems in hepatocytes by glucagon.Nature (London) 323:68–71

    Google Scholar 

  • Wasserman, S.I., Barrett, K.E., Huott, P.A., Beuerlein, G., Kagnoff, M.F., Dharmsathaphorn, K. 1988. Immune-related intestinal Cl− secretion I. Effect of histamine on the T84 cell line.Am. J. Physiol. 254:C53-C62

    PubMed  Google Scholar 

  • Weber, A. 1968. The mechanism of the action of caffeine on sarcoplasmic reticulum.J. Gen. Physiol. 52:760–772

    PubMed  Google Scholar 

  • Welsh, M.J., Smith, P.L., Frizzell, R.A. 1982. Chloride secretion by canine tracheal epithelium: II. The cellular electrical potential profile.J. Membrane Biol. 70:227–238

    Google Scholar 

  • Welsh, M.J., Smith, P.L., Frizzell, R.A. 1983. Chloride secretion by canine tracheal epithelium: III. Membrane resistances and electromotive forces.J. Membrane Biol. 71:209–218

    Google Scholar 

  • Yada, T., Oiki, S., Ueda, S., Okada, Y. 1986. Synchronous oscillation of the cytoplasmic Ca2+ concentration and membrane potential in cultured epithelial cells (Intestine 407).Biochim. Biophys. Acta 887:105–112

    PubMed  Google Scholar 

  • Yada, T., Okada, Y. 1984. Electrical activity of an intestinal epithelial cell line: Hyperpolarizing responses to intestinal secretagogues.J. Membrane Biol. 77:33–44

    Google Scholar 

  • Yada, T., Russo, L.L., Sharp, G.W.G. 1989. Phorbol ester-stimulated insulin secretion by RINm5F insulinoma cells is linked with depolarization and an increase in cytosolic free Ca2+ concentration.J. Biol. Chem. 264:2455–2462

    PubMed  Google Scholar 

  • Yamaguchi, D.T., Kleeman, C.R., Muallem, S. 1987. Protein kinase C-activated calcium channel in the osteoblast-like clonal osteosarcoma cell line UMR-106.J. Biol. Chem. 262:14967–14973

    PubMed  Google Scholar 

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  1. Toshihiko Yada

    Present address: Department of Physiology, Kagoshima University School of Medicine, 890, Kagoshima, Japan

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  1. Department of Physiology, Kyoto University Faculty of Medicine, 606, Kyoto, Japan

    Toshihiko Yada, Shigetoshi Oiki, Shunji Ueda & Yasunobu Okada

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  1. Toshihiko Yada
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Yada, T., Oiki, S., Ueda, S. et al. Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line. J. Membrain Biol. 112, 159–167 (1989). https://doi.org/10.1007/BF01871277

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