Abstract
The parasympathetic control of goblet cell secretion and the membrane events accompanying accelerated mucus release were studied in large intestinal mucosal biopsies maintained in an organ culture system. The secretory response of individual goblet cells to 10(-6) M acetylcholine chloride with 3 x 10(-3) M eserine sulfate (a cholinesterase inhibitor) was assessed by light microscopy and autoradiography, by scanning and transmission electron microscopy, and by freeze-fracture. Goblet cells on the mucosal surface are unaffected by acetylcholine. In crypt goblet cells acetylcholine-eserine induces rapid fusion of apical mucous granule membranes with the luminal plasma membrane (detectable by 2 min), followed by sequential, tandem fission of the pentalaminar, fused areas of adjacent mucous granule membranes. These events first involve the most central apical mucous granules, are then propagated to include peripheral granules, and finally spread toward the most basal granules. By 60 min, most crypt cells are nearly depleted. The apical membrane, although greatly amplified by these events, remains intact, and intracellular mucous granules do not coalesce with each other. During rapid secretion membrane-limited tags of cytoplasm are observed attached to the cavitated apical cell surface. These long, thin extensions of redundant apical membrane are rapidly lost, apparently by being shed into the crypt lumen.
Full Text
The Full Text of this article is available as a PDF (1.7 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahkong Q. F., Fisher D., Tampion W., Lucy J. A. Mechanisms of cell fusion. Nature. 1975 Jan 17;253(5488):194–195. doi: 10.1038/253194a0. [DOI] [PubMed] [Google Scholar]
- Amsterdam A., Ohad I., Schramm M. Dynamic changes in the ultrastructure of the acinar cell of the rat parotid gland during the secretory cycle. J Cell Biol. 1969 Jun;41(3):753–773. doi: 10.1083/jcb.41.3.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burwen S. J., Satir B. H. A freeze-fracture study of early membrane events during mast cell secretion. J Cell Biol. 1977 Jun;73(3):660–671. doi: 10.1083/jcb.73.3.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chandler D. E., Heuser J. Membrane fusion during secretion: cortical granule exocytosis in sex urchin eggs as studied by quick-freezing and freeze-fracture. J Cell Biol. 1979 Oct;83(1):91–108. doi: 10.1083/jcb.83.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chang W. W., Nadler N. J. Renewal of the epithelium in the descending colon of the mouse. IV. Cell population kinetics of vacuolated-columnar and mucous cells. Am J Anat. 1975 Sep;144(1):39–56. doi: 10.1002/aja.1001440104. [DOI] [PubMed] [Google Scholar]
- Chi E. Y., Lagunoff D., Koehler J. K. Freeze-fracture study of mast cell secretion. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2823–2827. doi: 10.1073/pnas.73.8.2823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Douglas W. W. Involvement of calcium in exocytosis and the exocytosis--vesiculation sequence. Biochem Soc Symp. 1974;(39):1–28. [PubMed] [Google Scholar]
- Eastwood G. L., Trier J. S. Organ culture of human rectal mucosa. Gastroenterology. 1973 Mar;64(3):375–382. [PubMed] [Google Scholar]
- Elliott H. L., Carpenter C. C., Sack R. B., Yardley J. H. Small bowel morphology in experimental canine cholera. A light and electron microscopic study. Lab Invest. 1970 Feb;22(2):112–120. [PubMed] [Google Scholar]
- FLOREY H. W. The secretion and function of intestinal mucus. Gastroenterology. 1962 Sep;43:326–329. [PubMed] [Google Scholar]
- Farquhar M. G. Recovery of surface membrane in anterior pituitary cells. Variations in traffic detected with anionic and cationic ferritin. J Cell Biol. 1978 Jun;77(3):R35–R42. doi: 10.1083/jcb.77.3.r35. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forstner G., Shih M., Lukie B. Cyclic AMP and intestinal glycoprotein synthesis: the effect of -adrenergic agents, theophylline, and dibutyryl cyclic AMP. Can J Physiol Pharmacol. 1973 Feb;51(2):122–129. doi: 10.1139/y73-016. [DOI] [PubMed] [Google Scholar]
- Forstner J. F. Intestinal mucins in health and disease. Digestion. 1978;17(3):234–263. doi: 10.1159/000198115. [DOI] [PubMed] [Google Scholar]
- Forstner J., Taichman N., Kalnins V., Forstner G. Intestinal goblet cell mucus: isolation and identification by immunofluorescence of a goblet cell glycoprotein. J Cell Sci. 1973 Mar;12(2):585–602. doi: 10.1242/jcs.12.2.585. [DOI] [PubMed] [Google Scholar]
- Freeman J. A. Goblet cell fine structure. Anat Rec. 1966 Jan;154(1):121–147. doi: 10.1002/ar.1091540111. [DOI] [PubMed] [Google Scholar]
- Friend D. S., Orci L., Perrelet A., Yanagimachi R. Membrane particle changes attending the acrosome reaction in guinea pig spermatozoa. J Cell Biol. 1977 Aug;74(2):561–577. doi: 10.1083/jcb.74.2.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gibbons R. J., Qureshi J. V. Selective binding of blood group-reactive salivary mucins by Streptococcus mutans and other oral organisms. Infect Immun. 1978 Dec;22(3):665–671. doi: 10.1128/iai.22.3.665-671.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hand A. R. The fine structure of von Ebner's gland of the rat. J Cell Biol. 1970 Feb;44(2):340–353. doi: 10.1083/jcb.44.2.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hasty D. L., Hay E. D. Freeze-fracture studies of the developing cell surface. II. Particle-free membrane blisters on glutaraldehyde-fixed corneal fibroblasts are artefacts. J Cell Biol. 1978 Sep;78(3):756–768. doi: 10.1083/jcb.78.3.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Herzog V., Farquhar M. G. Luminal membrane retrieved after exocytosis reaches most golgi cisternae in secretory cells. Proc Natl Acad Sci U S A. 1977 Nov;74(11):5073–5077. doi: 10.1073/pnas.74.11.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heuser J. E., Reese T. S., Dennis M. J., Jan Y., Jan L., Evans L. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J Cell Biol. 1979 May;81(2):275–300. doi: 10.1083/jcb.81.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hirsch J. G., Fedorko M. E. Ultrastructure of human leukocytes after simultaneous fixation with glutaraldehyde and osmium tetroxide and "postfixation" in uranyl acetate. J Cell Biol. 1968 Sep;38(3):615–627. doi: 10.1083/jcb.38.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- ICHIKAWA A. FINE STRUCTURAL CHANGES IN RESPONSE TO HORMONAL STIMULATION OF THE PERFUSED CANINE PANCREAS. J Cell Biol. 1965 Mar;24:369–385. doi: 10.1083/jcb.24.3.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jabbal I., Kells D. I., Forstner G., Forstner J. Human intestinal goblet cell mucin. Can J Biochem. 1976 Aug;54(8):707–716. doi: 10.1139/o76-102. [DOI] [PubMed] [Google Scholar]
- Karnovsky M. J. The ultrastructural basis of capillary permeability studied with peroxidase as a tracer. J Cell Biol. 1967 Oct;35(1):213–236. doi: 10.1083/jcb.35.1.213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim S. K., Nasjleti C. E., Han S. S. The secretion processes in mucous and serous secretory cells of the rat sublingual gland. J Ultrastruct Res. 1972 Feb;38(3):371–389. doi: 10.1016/s0022-5320(72)90012-3. [DOI] [PubMed] [Google Scholar]
- Lagunoff D. Membrane fusion during mast cell secretion. J Cell Biol. 1973 Apr;57(1):252–259. doi: 10.1083/jcb.57.1.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawson D., Raff M. C., Gomperts B., Fewtrell C., Gilula N. B. Molecular events during membrane fusion. A study of exocytosis in rat peritoneal mast cells. J Cell Biol. 1977 Feb;72(2):242–259. doi: 10.1083/jcb.72.2.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDermott R. P., Donaldson R. M., Jr, Trier J. S. Glycoprotein synthesis and secretion by mucosal biopsies of rabbit colon and human rectum. J Clin Invest. 1974 Sep;54(3):545–554. doi: 10.1172/JCI107791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moon H. W., Whipp S. C., Baetz A. L. Comparative effects of enterotoxins from Escherichia coli and Vibrio cholerae on rabbit and swine small intestine. Lab Invest. 1971 Aug;25(2):133–140. [PubMed] [Google Scholar]
- Neutra M. R., Grand R. J., Trier J. S. Glycoprotein synthesis, transport, and secretion by epithelial cells of human rectal mucosa: normal and cystic fibrosis. Lab Invest. 1977 May;36(5):535–546. [PubMed] [Google Scholar]
- Neutra M. R., Schaeffer S. F. Membrane interactions between adjacent mucols secretion granules. J Cell Biol. 1977 Sep;74(3):983–991. doi: 10.1083/jcb.74.3.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neutra M., Leblond C. P. Synthesis of the carbohydrate of mucus in the golgi complex as shown by electron microscope radioautography of goblet cells from rats injected with glucose-H3. J Cell Biol. 1966 Jul;30(1):119–136. doi: 10.1083/jcb.30.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orci L., Perrelet A., Friend D. S. Freeze-fracture of membrane fusions during exocytosis in pancreatic B-cells. J Cell Biol. 1977 Oct;75(1):23–30. doi: 10.1083/jcb.75.1.23. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palade G. E., Bruns R. R. Structural modulations of plasmalemmal vesicles. J Cell Biol. 1968 Jun;37(3):633–649. doi: 10.1083/jcb.37.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Palade G. Intracellular aspects of the process of protein synthesis. Science. 1975 Aug 1;189(4200):347–358. doi: 10.1126/science.1096303. [DOI] [PubMed] [Google Scholar]
- Satir B., Schooley C., Satir P. Membrane fusion in a model system. Mucocyst secretion in Tetrahymena. J Cell Biol. 1973 Jan;56(1):153–176. doi: 10.1083/jcb.56.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schantz A., Schecter A. Iron-hematoxylin and safranin O as a polychrome stain for epon sections. Stain Technol. 1965 Sep;40(5):279–282. doi: 10.3109/10520296509116427. [DOI] [PubMed] [Google Scholar]
- Stahl G. H., Ellis D. B. Biosynthesis of respiratory-tract mucins. A comparison of canine epithelial goblet-cell and submucosal-gland secretions. Biochem J. 1973 Dec;136(4):845–850. doi: 10.1042/bj1360845. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinberg S. E., Banwell J. G., Yardley J. H., Keusch G. T., Hendrix T. R. Comparison of secretory and histological effects of shigella and cholera enterotoxins in rabbit jejunum. Gastroenterology. 1975 Feb;68(2):309–317. [PubMed] [Google Scholar]
- Sturgess J., Reid L. An organ culture study of the effect of drugs on the secretory activity of the human bronchial submucosal gland. Clin Sci. 1972 Oct;43(4):533–543. doi: 10.1042/cs0430533. [DOI] [PubMed] [Google Scholar]
- Walker W. A. Host defense mechanisms in the gastrointestinal tract. Pediatrics. 1976 Jun;57(6):901–916. [PubMed] [Google Scholar]
- Yardley J. H., Bayless T. M., Luebbers E. H., Halsted C. H., Hendrix T. R. Goblet cell mucus in the small intestine. Findings after net fluid production due to cholera toxin and hypertonic solutions. Johns Hopkins Med J. 1972 Jul;131(1):1–10. [PubMed] [Google Scholar]