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Effects of verapamil on exocrine pancreatic secretion in man

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Abstract

Calcium ions are thought to mediate hormonal and cholinergic stimulation of exocrine pancreatic secretion. In order to further eludicate the role of calcium ions in stimulus-secretion coupling of the pancreas, the effect of the calcium antagonist verapamil, which inhibits transmembrane calcium influx, was studied on pancreatic secretion in 35 healthy male volunteers. Every subject had two stimulation periods of 2 hr each with a 3-hr period between the two. Pancreatic secretion was stimulated by cholecystokinin in 12 subjects, by secretin in 14 subjects, and by sham feeding in 6 subjects. Three subjects were studied without any secretory stimulus. Verapamil as an intravenous bolus of 150 μg/kg followed by an intravenous infusion of 150 μg/kg/hr or saline were given during the two 2-hr stimulation periods in a randomized order. The pancreatic secretory responses to stimulation by cholecystokinin, secretin, or sham feeding, as well as the basal pancreatic secretion without a secretory stimulus were left unaffected by verapamil when compared to the saline control. The results, therefore, call into question the hypothesis that transmembrane calcium influx is a major mediator of pancreatic secretion in response to hormonal or cholinergic stimulation in man.

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References

  1. Case R, Blausen T: The relationship between calcium exchange and enzyme secretion in the isolated rat pancreas. J Physiol 235:75–102, 1973

    Google Scholar 

  2. Gardner JC, Conlon TP, Klaeveman HL, Adams TD, Ondetti MA: Action of cholecystokinin and cholinergic agents on calcium transport in isolated pancreatic acinar cells. J Clin Invest 56:366–375, 1975

    Google Scholar 

  3. Kondo S, Schulz I: Calcium ion uptake in isolated pancreas cells induced by secretagogues. Biochim Biophys Acta 419:76–92, 1976

    Google Scholar 

  4. Schulz I, Milutinovic S, Heil K: The role of calcium and cyclic nucleotides in stimulus-secretion coupling.In Molecular Biology and Pharmacology of Cyclic Nucleotides. G Folco, R Paoletti (eds). Amsterdam, North-Holland, Elsevier Biomedical Press, 1978, pp 237–250

    Google Scholar 

  5. Singh M: Amylase release from dissociated mouse pancreatic acinar cells stimulated by glucagon: Effect of membrane stabilizers. J Physiol 302:81–91, 1980

    Google Scholar 

  6. Williams JA: Regulation of pancreatic acinar cell function by intracellular calcium. Am J Physiol 238:G269-G279, 1980

    Google Scholar 

  7. Hotz J, Minne H, Ziegler R: The influences of acute hyperand hypocalcemia and of calcitonin on exocrine pancreatic function in man. Res Exp Med 160:152–165, 1973

    Google Scholar 

  8. Goebell H, Steffen CH, Baltzer G, Bode CH: Stimulation of pancreatic secretion of enzymes by acute hypercalcemia in man. Eur J Clin Invest 3:98–104, 1973

    Google Scholar 

  9. Tiscornia O, Palasciano G, Dzieniszewski J, Verine H, Sarles H: Analysis of the mechanism of action of calcium-induced exocrine pancreatic secretory changes in the dog. Am J Gastroenterol 63:293–298, 1975

    Google Scholar 

  10. Malagelada JR, Holtermueller KH, Sizemore GW, Go VLW: The influence of hypercalcemia on basal and cholecystokinin-stimulated pancreatic, gallbladder, and gastric functions in man. Gastroenterology 71:405–408, 1976

    Google Scholar 

  11. Fleckenstein A: Pharmacology and electrophysiology of calcium antagonists.In Experience with Verapamil. A Zanchetti, DM Krikler (eds) Amsterdam, Exerpta Medica, 1980, pp 10–29

    Google Scholar 

  12. Eto S, McMillin Wood J, Hutchins M, Fleischer N: Pituitary45C++ and release of ACTH, GH, and TSH: Effect of verapamil. Am J Physiol 226:1315–1320, 1974

    Google Scholar 

  13. Malaisse WJ, Herchuelz A, Levy J, Sener A: Calcium antagonists and islet cell function—III. The possible site of action of verapamil. Biochem Pharmacol 26:735–740, 1977

    Google Scholar 

  14. De Marinis I, Parbarino A: Calcium antagonists and hormone release I. Effects of verapamil on insulin release in normal subjects and patients with islet cell tumor. Metabolism 29:599–603, 1980

    Google Scholar 

  15. Dominic JA, Miller RE, Anderson J, McAllister RG: Pharmacology of verapamil. II. Impairment of glucose tolerance by verapamil in the conscious dog. Pharmacology 20:196–205, 1980

    Google Scholar 

  16. Kierkegaard P, Christiansen J, Petersen B, Skovolsen P: Calcium and stimulus-secretion coupling in gastric fundic mucosa. Effect of inhibition of calcium transport by verapamil on gastric acid secretion in the isolated guinea pig fundic mucosa and in healthy subjects. Scand J Gastroenterol 17:533–538, 1982

    Google Scholar 

  17. Sonnenberg A, Kurosinski I, Eckhardt U, Scholten T: Verapamil inhibits gastric secretion stimulated by pentagastrin. Gastroenterology 84:A1316, 1983

    Google Scholar 

  18. Gersten M, Bank S, Burns G, Stein T, Zimmermann H: The effect of verapamil on pancreatic exocrine secretion. Gastroenterology 84:A1163, 1983

    Google Scholar 

  19. Newman J, Lewis BG, Swierczek JW, Sakamoto T, Townsend CM, Thompson JC: The effect of graded doses of verapamil on pancreatic exocrine secretion in awake dogs. Gastroenterology 84:A1259, 1983

    Google Scholar 

  20. Defilippi C, Solomon TE, Valenzuela JE: Pancreatic secretory response to sham feeding in humans. Digestion 23:217–223, 1982

    Google Scholar 

  21. Malawer SJ, Powell DW: An improved turbidimetric analysis of polyethylene glycol utilizing an emulsifier. Gastroenterology 53:250–256, 1967

    Google Scholar 

  22. Erlanger VF, Kokowsky N, Cohen W: The preparation and the proper ties of two new chromogenic substrates for trypsin. Arch Biochem 95:271–278, 1961

    Google Scholar 

  23. Nagel W, Willig F, Peschke W, Schmidt JH: Ueber die Bestimmung von Trypsin und Chymotrypsin mit Amino-p-nitroaniliden. Z Physiol Chem 340:1–10, 1965

    Google Scholar 

  24. Haegele EO, Schaich E, Rauscher E, Lehmann P, Grassl M: Action pattern of human pancreatic alpha-amylase on maltoheptaose. J Chromatogr 223:69–84, 1081

    Google Scholar 

  25. Lagerlof HO: Pancreatic function and disease. Acta Med Scand Suppl 128:1–13, 1942

    Google Scholar 

  26. Sung RJ, Meyerburg RJ, El-Sherif N, McAllister RG, Elser B, Castellanos A: Termination of supraventricular tachycardia by verapamil in man. Correlation of plasma drug levels with intracardiac electrophysiologic studies. Circulation (Suppl 2) 58:177, 1978

    Google Scholar 

  27. Eichelbaum M, Albrecht M, Kliems G, Schaefer K, Somogyi A: Influence of mesocaval shunt surgery on verapamil kinetics, bioavailability and response. Br J Clin Pharmacol 10:527–530, 1980

    Google Scholar 

  28. Clain JE, Barbezat GO, Marks IN: Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis. Gut 22:355–358, 1981

    Google Scholar 

  29. Regan PT, Malagelada JR, DiMagno EP: Duodenal calcium outputs in health and pancreatic disease. Gut 21:614–618, 1980

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine D, University of Duesseldorf, Germany

    Claus Niederau MD, Annelou Hellmann MD, Amnon Sonnenberg MD & Joachim Erckenbrecht MD

Authors
  1. Claus Niederau MD
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  2. Annelou Hellmann MD
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  3. Amnon Sonnenberg MD
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  4. Joachim Erckenbrecht MD
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Additional information

The authors were supported by a grant of the Deutsche Forschungsgemeinschaft (DFG-Ni 224/1-1).

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Niederau, C., Hellmann, A., Sonnenberg, A. et al. Effects of verapamil on exocrine pancreatic secretion in man. Digest Dis Sci 30, 72–77 (1985). https://doi.org/10.1007/BF01318374

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  • DOI: https://doi.org/10.1007/BF01318374

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