Summary
After the application of parachlorophenylalanine (pCPA), an amino acid analogue, paracrystalline inclusions are observed in the exocrine pancreas of the rat. The formation of the paracrystalline structures varies according to the dose and the time of examination. Although the first alterations can be seen in the Golgi apparatus and the condensing vacuoles, the main localization of these structures is within the cisternae of the RER. At the same time as degenerative changes occur in the cells, involving autophagic and heterophagic processes, regneration also takes place. With the freeze-fracturing method, the paracrystalline inclusions are interpreted as lamellae or plates of probably altered secretory proteins in extremely extended RER-cisternae. The fracture surfaces of the paracrystals show a periodicity of about 80 Å running diagonally to the main axis of the paracrystalline structures, which are mainly oriented from the basal parts of the exocrine pancreatic cells to the cell apices.
The mechanism of paracrystalline formation is discussed on the basis of the morphologic results. It could be shown that after pCPA administration the amylase content is decreased concomittantly with degranulation. pCPA seems not to be incorporated into secretory proteins; high intracellular concentrations, however, are required to induce the formation of the paracrystalline structures. This morphological study is the basis for other studies dealing with secretion and intracellular transport in the pancreatic acinar cell under experimental conditions.
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Bauduin, H., Tondeur, T., Van Sande, J., Vincent, D.: Secretion and protein metabolism in the rat pancreas in vitro. Biochim. biophys. Acta (Amst.) 304, 81–82 (1973)
Bernfeld, P.,: Amylases. In: Methods of Enzymology. Vol. 1, pp. 149–159. (S. Colowick and N. Kaplan, eds.) New York Academic Press: 1955
Bieger, W., Wacker, Ph., Forssmann, W.G.,: Zum Mechanismus der inhibierten Pankreassekretion durch p-Chlorophenylalanin (pCPA). Verh. Anat. Ges. 66, Anat. Anz. Ergh. 130, 87–97 (1972)
Blomquist, L.: Species differences in the accumulation of 4-iodophenylalanine in the exocrine pancreas. Comp. Biochem. Physiol. 28, 777–782, (1969)
Boquist, L.: The effect of excess methionine on the pancreas. Lab. Invest. 21, 96–104 (1969)
Caro, L.G., Palade, G.E.: Protein synthesis, storage and discharge in the pancreatic exocrine cell. J. Cell Biol. 20, 473–495 (1964)
Dabrunz, R., Forssmann, W.G.,: Sekretionsstudien am exokrinen Pankreas nach Stimulation mit Caerulein. Verh. Anat. Ges. 66, Ergh. Anat. Anz. 130, 99–108 (1972)
Forssmann, W.G.: A method for in vivo diffusion tracer studies combining perfusion fixation with intravenous tracer injection. Histochemie 20, 277–286 (1969)
Forssmann, W.G., Bieger, W.: Biosynthese falscher Proteine: Einbau von p-Chlorophenylalanin in Enzyme des exokrinen Pankreas. Res. exp. Med. 160, 1–20 (1973)
Forssmann, W.G., Bieger, W., Roth, M.,: Untersuchungen der falschen Proteinsynthese im exokrinen Pankreas. Verh. Anat. Ges., 67, Anat. Anz. Ergh., 132, 507–515 (1973)
Forssmann, W.G., Wacker, Ph., Daldrup, J., Tesi, D., Rouiller, Ch.,: Paracrystalline inclusions in the granular endoplasmic reticulum of exocrine pancreas after treatment with para-chlorophenylalanine. In: 7. Internat. Congr. Electr. Microsc., Grenoble, Vol. III (P. Farvard, ed.), pp. 505–506, 1970
Gal, E.M.: Molecular basis of inhibition of monoxygenases by p-halophenylalanines. Adv. Biochem. Psychopharmacol. 6, 149–163 (1972)
Herman, L., Fitzgerald, P.J.: The degenerative changes in pancreatic acinar cells caused by DLethionine. J. Cell Biol. 12, 277–296 (1962)
Hruban, Z., Swift, H., Wissler, R.W.: Analog-induced inclusions in pancreatic acinar cells. J. Ultrastr. Res. 7, 273–285 (1962)
Jamieson, J.D., Palade, G.E.: Intracellular transport of secretory proteins in the pancreatic cell. II. Transport to condensing vacuoles and zymogen granules. J. Cell Biol. 34, 597–615 (1967b)
Jamieson, J.D., Palade, G.E.: Synthesis, intracellular transport and distribution of secretory proteins in stimulated pancreatic exocrine cell. J. Cell Biol. 50, 135–147 (1971)
Jequier, E., Lovenberg, W., Sjoerdesma, A.: Tryptophan hydroxylase inhibition: the mechanism by which p-chlorophenylalanine depletes rat brain serotonin. Med. Pharmacol. 3, 274–278 (1967)
Jouvet, M.: Biogenic amines and the states of sleep. Science 163, 32–41 (1969)
Kaufman, N., Klavins, J.V., Kinney, T.D.: Pancreatic damage induced by excess methionine. Arch. Path. (Chic.) 70, 331 (1960)
Koe, B.K., Weissman, A.: p-chlorophenylalanine: a specific depletor of brain serotonin. J. Pharmacol. exp. Therap. 154, 499–516 (1966)
Koella, W.P., Feldstein, H., Cziman, J.: The effect of parachlorophenyl-alanine on sleep of cats. Electroenceph. Clin. Neurophysiol. 25, 481–490 (1968)
Lambert, M., Cannes, J., Christophe, J.: Pancreozymin and caerulein stimulate in vitro protein phosphorylation in the rat pancreas. Biochem. biophys. Res. Commun. 52, 935–952 (1973)
Leroy, J., Morisset, J.A., Webster, P.D.: Dose related response of pancreatic synthesis and secretion to cholecystokinin-pancreozymin. J. Lab. clin. Med. 78, 149–157 (1971)
Lowry, Oh.H., Rosebrough, N.J., Farr, A.L., Randall, R.J.: Protein measurement with the folinphenol reagent. J. biol. Chem. 193, 265–275 (1951)
Luft, J.H.: Improvements in epoxy resin embedding methods. J. biophys. Biochem. Cytol. 9, 409–414 (1961)
Malmnäs, C.O., Meyerson, B.J.: p-chlorophenylalanine and copulatory behavior in the male rat. Nature (Lond.) 232, 398–400 (1971)
Metz, J., Brühl, U., Taugner, R., Forssmann, W.G.: Feinstruktur von pCPA anreichernden Organen. Verh. Anat. Ges. 68, Anat. Anz. Ergh. 134, 653–662 (1974)
Metz, J., Forssmann, W.G.: Exocrine pancreas under experimental conditions. II. Synthesis, intracellular transport, and discharge of secretory proteins in pCPA treated pancreatic exocrine cells. (In press)
Moor, H., Mühlethaler, K.: Fine structure in frozen etched yeast cells. J. Cell Biol. 17, 609–628 (1963)
Morisset, J.A., Webster, P.D.,: In vitro and in vivo effects of pancreozymin, urocholine, and cyclic AMP on rat pancreas. Amer. J. Physiol. 230, 202–208, 1971
Orci, L., Perrelet, A., Like, A.A.: Fenestrae in the rough endoplasmic reticulum of the exocrine pancreatic cells. J. Cell Biol. 55, 245–249 (1972)
Rauterberg, W., Vogel, H., Forssmann, W.G.: Exocrine pancreas under experimental conditions. V. DNA nuclear labelling and regeneration of the pCPA treated exocrine pancreas. (In prep.)
Reynolds, E.S.: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J. Cell Biol. 17, 208–212 (1963)
Schneider, W.C.: Phosphorus compounds in animal tissues. I. Extraction and estimation of desoxypentose nucleic acid and pentose nucleic acid. J. biol. Chem. 161, 293–297 (1945)
Singh, M., Black, O., Webster, P.D.: Effect of drugs on pancreatic amylase secretion in vitro. Gastroenterol. 63, 449–457 (1972)
Singh, M., Black, O., Webster, P.D.: Effect of selected drugs on pancreatic macromolecular transport. Gastroenterol. 64, 983–991 (1973)
Tagliamonte, A., Tagliamonte, P., Gessa, G.L., Brooke, B.B.: Compulsive sexual activity induced by p-chlorophenylalanine in normal and pinealectomized male rats. Scince 166, 1433–1435 (1965)
Vincent, D., Bauduin, H.: Influence de la céruléine sur la sécrétion et le métabolisme du pancréas exocrine du rat in vitro. Biol. Gastroent. V, 85–90 (1972)
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We are very grateful to Mrs. B. Brühl, Mrs. I. Stenull and cand. med. P. Zahn for technical assistence. We also gratefully acknowledge Prof. Dr. R. Taugner for the help with freeze-fracturing
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Forssmann, W.G., Metz, J. Exocrine pancreas under experimental conditions. Cell Tissue Res. 171, 467–482 (1976). https://doi.org/10.1007/BF00220239
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DOI: https://doi.org/10.1007/BF00220239