Abstract
The effect of the inflammatory mediator bradykinin on glycoprotein synthesis and mucin secretion in the human colonic adenocarcinoma cell line HT29–18N2 was examined. Bradykinin, at a threshold of 0.01 μM, accelerated the rate of mucin discharge as assessed by a mucin-specific ELISA. Using immunofluorescence microscopy, a thick meshwork of extracellular mucus was observed over bradykinin-treated monolayers but not mock-treated controls. Morphometric analysis of bradykinin-treated monolayers revealed no decreases in intracellular mucin stores or any other easily discernable morphological alteration. The ability of the cyclooxygenase inhibitors indomethacin and naproxen to decrease the response to bradykinin by approximately 68% indicates the effect is mediated, at least partially, through the generation of prostaglandins. Bradykinin did not alter the rate of incorporation of3H-glucosamine into newly synthesized glycoproteins. Bradykinin-accelerated mucin secretion may be linked to the depletion of intracellular mucin stores in the inflammatory bowel disease ulcerative colitis.
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T. S. Gaginella and J. F. Kachur,Kinins as mediators of intestinal secretion. Am. J. Physiol.256, G1-G15 (1989).
I. J. Zeitlen,Kinin release associated with the gastrointestinal tract. J. Adv. Exp. Med. Biol.8, 329–339 (1970).
I. J. Zeitlin and A. N. Smith,Mobilization of tissue kallikrein in inflammatory diseases of the colon. Gut14, 133–138 (1973).
D. A. Malatjalian,Pathology of inflammatory bowel disease in colorectal mucosal biopsies, Dig. Dis. Sci.32, 5S-15S, 1987.
A. P. Baker, L. M. Hillegass, D. A. Holden and W. J. Smith,Effect of kallidin, substance P, and other basic polypeptides on the production of respiratory macromolecules. Am. Rev. Respir. Dis.115, 811–817 (1977).
J. N. Baraniuk, P. B. Silver, M. A. Kaliner and P. J. Barnes,Ibuprofen augments bradykinin-induced glycoconjugate secretion by human nasal mucosa in vivo. J. Allergy Clin. Immunol.89, 1032–1039 (1992).
D. A. Baron, D. H. Miller and H. S. Margolius,Kinins induce rapid structural changes in colon concomitant with chloride secretion, Cell Tissue Res.246, 589–594 (1986).
T. E. Phillips, C. Huet, P. R. Bilbo, D. K. Podolsky, D. Louvard and M. R. Neutra,Human intestinal, goblet cells in monolayer culture: Characterization of mucus-secreting subclone derived from the HT29 colon adenocarcinoma cell line. Gastroenterology94(6), 1390–1403 (1988).
T. E. Phillips, C. M. Stanley, and J. Wilson,The effect of 16,16-dimethyl prostaglandin E 2 on proliferation of an intestinal goblet cell line and its synthesis and secretion of mucin glycoproteins. Prostaglandins Leukotrienes and Essential Fatty Acids48, 423–428 (1993).
T. E. Phillips and J. Wilson,Signal transduction pathways mediating mucin secretion from intestinal goblet cells, Dig. Dis. Sci.38, 1046–1054 (1993).
D. J. McCool, M. A. Marcon and G. Forstner,The T84 human colonic adenocarcinoma cell line produces mucin in culture and releases it in response to various secretagogues. Biochem. J.267, 491–500 (1990).
E. B. Frisch and T. E. Phillips,Lectin binding patterns to plasmalemmal glycoconjugates of goblet cells undergoing differentiation in vitro. J. Electron Microscopy Techniques16(1), 25–36 (1990).
G. Herbener, R. Goodfliesh and B. Fass-Holmes,A microcomputer program for evaluating sampling error: An application to stereological methods for electron microscopy. Biotech. Histochem.67(3), 165–170 (1992).
R. D. Specian and M. R. Neutra,Regulation of intestinal goblet cell secretion. I. Role of parasympathetic innervation. Am. J. Physiol.242, G370-G379 (1982).
T. E. Phillips,Both crypt and villus intestinal goblet cells secrete mucin in response to cholinergic stimulation. Am. J. Physiol.262(25), G327-G331 (1992).
T. E. Phillips and J. Wilson,Morphometric analysis of mucous granule depletion and replenishment in rat colon. Dig. Dis. Sci.38, 2299–2304 (1993).
M. W. Musch, J. F. Kachur, R. J. Miller, M. Field and J. S. Stoff,Bradykinin-stimulated electroyte secretion in rabbit and guinea pig intestine: involvement of arachidonic acid metabolism. J. Clin. Invest.71, 1073–1083 (1983).
S. A. Hojvat, M. W. Musch and R. J. Miller,Stimulation of prostaglandin production in rabbit ileal mucosa by bradykinin. J. Pharmacol. Exp. Therap.266, 749–755 (1983).
R. D. Zipser, J. B. Patterson, H. Kao, C. J. Hauser and R. Locke,Hypersensitive prostaglandin and thromboxane responses to hormones in rabbit colitis. Am. J. Physiol.249, G457-G463 (1985).
L. D. Lawson and D. W. Powell,Bradykinin-stimulated eicosanoid synthesis and secretion by rabbit ileal components. Am. J. Physiol.252, G783-G790 (1987).
G. Warhurst, M. Lees, N. B. Higgs and L. A. Turnberg,Site and mechanisms of action of kinins in rat ileal mucosa. Am. J. Physiol.252, G293-G300 (1987).
A. W. Cuthbert, S. C. Kirkland and L. J. MacVinnish,Kinin effects on ion transport in monolayers of HCA-7 cells, a line from a human colon adenocarcinoma, Br. J. Pharmacol.86, 3–5 (1985).
M. R. Neutra, R. J. Grand and J. S. Trier,Glycoprotein synthesis, transport, and secretion by epithelial cells of human rectal mucosa. Lab. Invest.36, 535–546 (1977).
B. S. McAllister, L. M. F. Leeb-Lundberg, M. A. Javors and M. S. Olson,Bradykinin receptors and signal transduction pathways in human fibroblasts: Integral role for extracellular calcium. Arch. Biochem. Biophys.304, 294–301 (1993).
C. Emond, J. L. Bascands, C. Pecher, G. Cabos-Boutot, P. Pradelles, D. Regoli and J. P. Girolami,Characterization of a B 2-bradykinin receptor in rat renal mesangial cells. Eur. J. Pharmacol.190, 381–392 (1990).
A. W. Baird, D. H. Miller, D. A. Schwartz and H. S. Margolius,Enhancement of kallikrein production and kinin sensitivity in T84 cells by growth in the nude mouse. Am. J. Physiol.261, C822-C827 (1991).
A. W. Cuthbert, A. M. George and L. MacVinish,Kinin effects on electrogenic ion transport in primary cultures of pig renal papillary collecting tubule cells. Am. J. Physiol.249, F439-F497 (1985).
A. W. Cuthbert and H. S. Margolius,Kinins stimulate net chloride secretion by rat colon. Br. J. Pharmacol.75, 587–598 (1982).
H. M. Berschneider and D. W. Powell,Fibroblasts modulate intestinal secretory response to inflammatory mediators. J. Clin. Invest.89, 484–489 (1992).
D. K. Podolsky and K. J. Isselbacher,Glycoprotein composition of colonic mucosa: Specific alterations, in ulcerative colitis. Gastroenterology87, 991–998 (1984).
D. K. Podolsky and D. A. Fournier,Alterations in mucosal content of colonic glycoconjugates in inflammatory bowel disease defined by monoclonal antibodies. Gastroenterology95, 379–387 (1988).
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Stanley, C.M., Phillips, T.E. Bradykinin modulates mucin secretion but not synthesis from an intestinal goblet cell line. Agents and Actions 42, 141–145 (1994). https://doi.org/10.1007/BF01983480
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DOI: https://doi.org/10.1007/BF01983480