Skip to main content
Log in

Vasoactive intestinal peptide (VIP)-induced enzyme secretion in rat pancreatic tissue is not associated with activation of nitric oxide synthase (NOS) and increase in cyclic GMP level

  • Research Articles
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin- pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seoet al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References Cited

  • Bennett, M. A., Watt, P. A. C. and Thurston, H., Endothelium-dependent modulation of resistance vessel contraction: studies with NG-nitro-L arginine methyl ester and NG-nitro-L-arginine.Br. J. Pharmacol., 107, 616–621 (1992).

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Bradford, M. E., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principles of protein-dye binding.Anal. Biochem., 42, 248–254 (1976).

    Article  Google Scholar 

  • Bredt, D. S. and Snyder, S. H., Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.Proc. Natl. Acad. Sci. USA, 87, 682–685 (1990).

    Article  PubMed  CAS  Google Scholar 

  • Christophe, J. P., Frandsen, E. K., Conlon, T. P., Krishna, G. and Gardner, J. D., Action of cholecystokinin, cholinergic agents and A-23187 on accumulation of guanosine 3′,5′-monophosphate in dispersed guinea pig pancreatic acinar cells.J. Biol. Chem., 251, 4640 (1976).

    PubMed  CAS  Google Scholar 

  • Garbers, D. L., Guanylyl cyclase receptors and their endocrine, paracrine, and autocrine ligands.Cell, 74, 1–4 (1992).

    Google Scholar 

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

    CAS  Google Scholar 

  • Haymovis, A. and Scheele, G. A., Cellular cyclic nucleotides and enzyme secretion in the pancreatic acinar cells.Proc. Natl. Acad. Sci. U.S.A., 73, 156 (1976).

    Article  Google Scholar 

  • Holst, J. J., Fahrenkrug, J., Knuhtsen, S., Jensen, S. L., Poulsen, S. S. and Nielsen, O. V., Vasoactive intestinal polypeptide (VIP) in the pig pancreas: role of VIPergic nerves in control of fluid and bicarbonate secretion.Regulatory Peptide, 8, 245, 245–259 (1984).

    Article  CAS  Google Scholar 

  • Holst, J. J., Schaffalitzky De Muckadell, O. B. and Fahrenkrug, J., Nervous control of pancreatic exocrine secretion in pigs.Acta physio. scand., 105, 33–51 (1979).

    Article  CAS  Google Scholar 

  • Iwatsuki, K., Iijima, F., Yamagishi, F. and Chiba, S., Effects of nitroprusside on pancreatic secretion and cyclic nucleotide concentration in the dog pancreas.European J. of pharmacol., 123, 307–309 (1986).

    Article  CAS  Google Scholar 

  • Kiechle, F. L. and Malinski, T., Nitric Oxide Biochemistry, Pathophysiology and detection.Am. J. Clin. Pathol., 100, 567–575 (1993).

    PubMed  CAS  Google Scholar 

  • Kruk, Z. L. and Pycock, C. J.,Neurotransmitters and drugs. Chapman & Hall, 1991.

  • Meyer-Alber, A., Fetz, I., Waschulewski, I. H., Höcker, M., Foölsch, U. R. and Schmidt, W. E., Calyculin A, okadaic acid and W-7 interfere with a distal step in pancreatic acinar signal transductionBiochem. Biophys. Res. Commun., 201, 1470–1476 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Nathan, C. and Xie, Q.-w., Nitric oxide synthases: roles, tolls, and controls.Cell, 78, 915–918 (1994).

    Article  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 cells.J. Biol. Chem., 265, 12846–12853 (1990).

    PubMed  CAS  Google Scholar 

  • Schmidt, H. H. H. W. and Walter, U., NO at work.cell, 78, 919–925 (1994).

    Article  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.Archives of Pharmacal Research, 18, 434–439 (1995).

    Article  CAS  Google Scholar 

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

  • Schulz, I. and Stolz, H. H., The exocrine pancreas: the role of secretagogues, cyclic nucleotides and calcium in enzyme secretion.Ann. Rev. Physiol., 239, 127–156 (1980).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nam, T.K., Han, J.w., Nam, S.W. et al. Vasoactive intestinal peptide (VIP)-induced enzyme secretion in rat pancreatic tissue is not associated with activation of nitric oxide synthase (NOS) and increase in cyclic GMP level. Arch. Pharm. Res. 19, 201–206 (1996). https://doi.org/10.1007/BF02976890

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02976890

Key word

Navigation