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NO/cGMP pathway is involved in exocrine secretion from rat pancreatic acinar cells

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Abstract

The enzyme responsible for the synthesis of nitric oxide (NO) from L-arginine in mammalian tissues is known as nitric oxide synthase (NOS) (EC.1.14.13.39). In the present study, the role of NO in the regulation of exocrine secretion was investigated in rat pancreatic acinar cells. Treatment of rat pancreatic acinar cells with cholecystokinin-octapeptide (CCK-OP) resulted in an increase in the arginine conversion to citrulline, the amount of NOx, the release of amylase, and the level of cGMP. Especially, CCK-OP-stimulated increase of arginine to citrulline transformation, the amount of NOx and cGMP level were completely counteracted by the inhibitor of NOS, NG-monomethyl-L-arginine (MMA), by contrast, that of amylase release was partially reduced. Furthermore, MMA-induced decrease of NOS activity and amylase release showed dose-dependent pattern. The data on the time course of CCK-OP-induced citrulline formation and cGMP rise indicate that NOS and guanylate cyclase were activated by treatment of CCK-OP. However, the mechanism of agonist-stimulated guanylate cyclase activation in acinar cells remains unknown. Therefore, activation of NOS is one of the early events in receptor-mediated cascade of reactions in pancreatic acinar cells and NO, not completely, but partially mediate pancreatic enzyme exocrine secretion.

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References Cited

  • Bernfeld, P., Amylases, α and β.Method in Enzymol., 1, 149–158 (1955).

    Article  CAS  Google Scholar 

  • Cox, R. D., Determination of nitrate and nitrite at the parts or billion level by chemiluminescence.Anal. Chem., 52, 332–335 (1980).

    Article  CAS  Google Scholar 

  • Gukovskaya, A. S. and Pandol, S. J., Nitric oxide production regulates cGMP formation and calcium influx in pancreatic acinar cells.Am. J. Physiol., 266, G350-G356 (1994).

    PubMed  CAS  Google Scholar 

  • Gukovskaya, A. S. and Pandol, S. J., Nitric oxide regulates neurotransmitter induced cGMP rise and Ca2+ influx in pancreatic acinar cells.Gastroenterology, 104, A306 (1993).

    Google Scholar 

  • Yoshida, H., Tsunoda, Y. and Owyang, C., Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca2+ entry and amylase secretion from the rat pancreas.Pflugers Arch-Eur. J. Physiol., 434, 25–37 (1997).

    Article  CAS  Google Scholar 

  • Ignarro, L. J., Bugo, G. M., Byrns, R. E. and Chaudhuri, G., Endothelium-derived relaxing factor produced and released form artery and vein is nitric oxide.Proc. Natl. Acad. Sci. USA, 84, 9265–9269 (1987).

    Article  PubMed  CAS  Google Scholar 

  • Moncada, S., Palmer, R. M. J. and Higgs, E. A., Nitric oxide: physiology and pharmacology.Pharmacol. Rev., 44, 109–14241 (1991).

    Google Scholar 

  • Muallem, S., Calcium transport pathways of pancreatic acinar cells.Annu. Rev. Physiol., 51, 83–105 (1989).

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. and Hibbs, J. B., Role of nitric oxide synthasis in macrophage antimicrobial activity.Curr. Opin. Immunol., 3, 65–70 (1991).

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. and Xie, Q. W., Regulation of Biosynthesis of Nitric Oxide.J. Biol. Chem., 269(19), 13725–13728 (1994).

    PubMed  CAS  Google Scholar 

  • Pandol, S. J. and Schoeffield-Payne, M. S., Cyclic GMP mediates the agonist-stimulated increase in plasma membrane calcium entry in the pancreatic acinar cell.J. Biol. Chem., 265, 12846–12853 (1990).

    PubMed  CAS  Google Scholar 

  • Seo, D. W., Nam, S. W., Nam, T. K., Lee, Y. J., Ko, Y. K. and Lee, H. W., Effect of Cholecystokinin-pancreozymin on the Nitric Oxide Synthase Activity and cyclic GMP level in rat pancreatic tissue.Arch. Pharm. Res., 18, 434–439 (1995).

    Article  CAS  Google Scholar 

  • Solomon, T. E., Control of exocrine pancreatic secretion. In: Physiology of the Gastrointestinal tract, 2, 1173–1208 (1987).

  • Williams, J. A., Korc, M. and Dormer, R., Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini.Am. J. Physiol., 4(5), E517-E524 (1978).

    Google Scholar 

  • Wrenn, R. W., Currie, M. G. and Herman, L. E., Nitric oxide participate in the regulation of pancreatic acinar cell secretion.Life Science, 55, N.7. 511–518 (1993).

    Article  Google Scholar 

  • Xu, X., Star, R. A., Tortorici, G. and Muallem, S., Depletion of intracellular Ca2+ stores activates nitricoxide synthase to generate cGMP and regulate Ca2+ influx.J. Biol. Chem., 269, 12645–12653 (1994).

    PubMed  CAS  Google Scholar 

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Ahn, SH., Seo, DW., Ko, YK. et al. NO/cGMP pathway is involved in exocrine secretion from rat pancreatic acinar cells. Arch. Pharm. Res. 21, 657–663 (1998). https://doi.org/10.1007/BF02976753

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