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Morphological studies by light and electron microscopy of pancreatic acinar cells under the effect of Tityus serrulatus venom


We studied in vivo and in vitro morphological aspects of pancreatic acinar cells after treatment with Tityus serrulatus venom (TSV). After three hours in an in vitro system, positive secretagogue effects of the venom were identifiable both at the light-microscopic (LM) and the electron-microscopic (EM) levels. At 1 μg/ml TSV, maximal secretion (as measured in a concomitant radiolabeling dose-response experiment) of exocrine proteins at 58% was manifest as a discharge of most zymogen granules (ZG) and consequent appearance of secretory material in acinar lumina. At the supramaximal dose of 10 μg/ml TSV, exocytotic images were often observed also with secretory contents previously discharged. The lowest dose of venom at 0.01 μg/ml caused no stimulation of zymogen discharge above resting secretion levels; however, morphological changes were observed. At high doses of TSV, both in vivo and in vitro, large aggregates associated with the cis-Golgi develop between this region and the endoplasmic reticulum (ER). Since Tityus venoms have been associated with causation of pancreatitis, we were interested in comparisons of our experimental tissue with parameters attributed to development of the disease. Our studies have demonstrated considerable evidence that large intracellular vacuoles, discharged ZG, effaced acinar lumina with disappearance of microvilli and other manifestations of possible early events in pancreatitis are indeed frequently observed both in pancreatic lobules in vitro and in whole pancreas in vivo when exposed to TSV.

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  1. Adler G, Hupp T, Kern HT (1979) Course and spontaneous regression of acute pancreatitis in the rat. Virchows Arch [A] 382:31–47

  2. Aho HJ, Nevalainen TJ, Havia VT, Heinonen RJ, Aho AJ (1982) Human acute pancreatitis: A light and electron microscopic study. Acta Pathol Microbiol Immunol Scand Sect A 90:367–373

  3. Bartholomew C (1970) Acute scorpion pancreatitis in Trinidad. Br Med J 1:666–668

  4. Bernfeld P (1955) Amylases, α and β. In: Colowick SP, Kaplan NO (eds) Methods in enzymology, vol I. Academic Press, New York, pp 149–158

  5. Bohm GM, Pompolo S, Diniz CR, Gomez MV, Pimenta AF, Netto JC (1974) Ultrastructural alterations of mouse diaphragm nerve endings induced by purified scorpion venom tityustoxin. Toxicon 12:509–511

  6. Corrado AP, Neto FR, Antonio A (1974) The mechanism of the hypertensive effect of Brazilian scorpion venom (Tityus serrulatus Lutz and Mello). Toxicon 12:145–150

  7. Diniz CR (1971) Clinical and pharmacological properties of Tityus venoms. In: Bucherl W, Buckley EE (eds) Venomous animals and their venoms. Venomous invertebrates, vol III. Academic Press, New York, pp 311–315

  8. Fletcher PL Jr, Fletcher MD, Possani LD (1992) Characteristics of pancreatic exocrine secretion procuced by venom from the Brazilian scorpion Tityus serrulatus. Eur J Cell Biol 58:259–270

  9. Freire-Maia L, Azevedo AD, Costa Val VP (1973) Respiratory arrhythmias produced by purified scorpion toxin. Toxicon 11:255–257

  10. Freire-Maia L, Pinto GI, Franco I (1974) Mechanism of the cardiovascular effects produced by purified scorpion toxin in the rat. J Pharmacol Exper Ther 188:207–213

  11. Rreire-Maia L, Azevedo AD, Lima EG (1976 a) Pharmacological blockade of the cardiovascular and respiratory effects produced by Tityustoxin in the rat. In: Ohsaka A, Hayashi K, Sawai Y (eds) Animal plant and microbial toxins, vol 2. Plenum Press, New York, pp 287–298

  12. Freire-Maia L, Cunha-Melo JR, Futuro-Neto HA, Azevedo AD, Weinberg J (1976 b) Cholinergic and adrenergic effects of Tityustoxin. Gen Pharmacol 7:115–121

  13. Freire-Maia L, Cunha-Melo JR, Gomez MV, Maria TA, Calixto SL, Futuro-Neto HA (1976 c) Studies on the mechanism of action of Tityustoxin. In: Ohsaka A, Hayashi K, Sawai Y (eds) Animal plant and microbial toxins, vol 2. Plenum Press, New York, pp 273–285

  14. Hendricks LC, McCaffery M, Palade GE, Farquhar MG (1993) Disruption of endoplasmic reticulum to Golgi transport leads to the accumulation of large aggregates containing β-COP in pancreatic acinar cells. Mol Biol Cell 4:413–424

  15. Kloppel G, Dreyer T, Willemer S, Kern H, Adler G (1986) Human acute pancreatitis: its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells. Virchows Arch [A] 409:791–803

  16. Kulka RG, Sternlicht E (1968) Enzyme secretion in mouse pancreas mediated by adenosine-3′5′-cyclic phosphate and inhibited by adenosine-3′-phosphate. Proc Natl Acad Sci USA 61:1123–1128

  17. Lampel M, Kern H (1977) Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch [A] 373:97–117

  18. Lima EG, Almeida HO, Gomez MV, Freire-Maia L (1975) Acute pulmonary edema induced by injection of Tityustoxin into the lateral ventricles of rats. Toxicon 13:205–206

  19. Machado JC, Silveira JF da (1977) Induction of acute hemornhagic pancreatitis in dog by escorpionic venom of T. serrulatus. Mem Inst Butantan 40/41:1–9

  20. Merisko EM, Fletcher M, Palade GE (1986) The reorganization of the Golgi complex in anoxic pancreatic cells. Pancreas 1:95–109

  21. Novaes G, Catanzaro OL, Beraldo WT, Freire-Maia L (1982) Effect of purified scorpion toxin (Tityustoxin) on the pancreatic secretion of the rat. Toxicon 20:847–853

  22. Oprins A, Duden R, Kreis TE, Geuze HJ, Slot JW (1993) β-COP localizes mainly to the cis-Golgi side in exocrine pancreas. J Cell Biol 121:49–59

  23. Pantoja JL, Renner IG, Abramson SB, Edmonson HA (1983) Production of acute hemorrhagic pancreatitis in the dog using venom of the scorpion Buthus quinquestriatus. Dig Dis Sci 28:429–439

  24. Poon-King T (1963) Myocarditis from scorpion stings. Br Med J 1:374

  25. Possani LD (1984) Structure of scorpion toxins. In: Tu AT (ed) Handbook of natural toxins, vol II. Marcel Dekker, New York, pp 513–550

  26. Possani LD, Alagon AC, Fletcher PL Jr, Erickson BW (1977) Purification and properties of mammalian toxins from the venom of the Brazilian scorpion Tityus serrulatus Lutz and Mello. Arch Biochem Biophys 180:394–403

  27. Possani LD, Martin BM, Fletcher MD, Fletcher PL Jr (1991) Discharge effect on pancreatic exocrine secretion produced by toxins purified from Tityus serrulatus scorpion venom. J Biol Chem 266:3178–3185

  28. Rossi MA, Ferreira AL, Paiva SM (1974) Fine structures of pulmonary changes induced by Brazilian scorpion venom. Arch Pathol 97:284–288

  29. Scheele GA, Palade GE (1975) Studies on the guinea pig pancreas. Parallel discharge of exocrine enzyme activities. J Biol Chem 250:2660–2770

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

  31. Sofer S, Shalev H, Weizman Z, Shahak E, Gueron M (1991) Acute pancreatitis in children following envenomation by the yellow scorpion Leiurus quinquestriatus. Toxicon 29:125–128

  32. Tafuri WL, Maria TA, Freire-Maia L, Cunha-Melo JR (1974) Effect of the scorpion toxin on the granular vesicles in the Auerbach's plexus of the rat ileum. J Neural Trans 35:233–240

  33. Vincent D, Bauduin H (1972) Influence of cerulein on the secretion and metabolism of the rat exocrine pancreas in vitro. Biol Gastroenterol 5:85–90

  34. Watanabe O, Baccino FM, Steer ML, Meldolesi J (1984) Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis. Am J Physiol 246:G457–467

  35. Waterman JA (1938) Some notes on scorpion poisoning in Trinidad. Trans R Soc Trop Med Hyg 31:607–624

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Fletcher, M.D., Possani, L.D. & Fletcher, P.L. Morphological studies by light and electron microscopy of pancreatic acinar cells under the effect of Tityus serrulatus venom. Cell Tissue Res. 278, 255–264 (1994). https://doi.org/10.1007/BF00414168

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Key words

  • Scorpion venom
  • Exocrine pancreas
  • Secretagogue
  • Electron microscopy
  • Pancreatitis
  • cis-Golgi aggregates