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Bile Secretion Is Centrally Regulated by C-Type Natriuretic Peptide

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Abstract

1. Current evidence supports that C-type natriuretic peptide (CNP) is the brain natriuretic peptide. Natriuretic peptide receptors and mRNA CNP have been reported in the liver and in discrete areas and nucleus of the central nervous system involved in the regulation of gastrointestinal physiology. In the present work, we sought to establish the role of CNP in the central regulation of bile secretion in the rat and to delineate the possible pathways and mechanisms involved.

2. To examine the role of CNP on bile secretion, the peptide was applied in the brain lateral ventricle (1, 10, and 100 ng/μL) and bile samples were collected every 15 min for 60 min. The role of the autonomic nervous system in CNP response was assessed by atropine or combined phentolamine and propranolol administration.

3. Centrally applied CNP diminished basal as well as bile salt-evoked bile flow in a dose-dependent manner. CNP reduced bile acid output as well as sodium and potassium excretion, supporting CNP effect on bile acid-dependent flow. CNP also decreased chloride excretion and increased bile pH. The excretion of total glutathione was not affected by centrally applied CNP suggesting that this peptide does not alter bile acid-independent flow. Neither parasympathetic nor sympathetic blockade abolished CNP inhibitory response on bile secretion. Mean arterial pressure and portal venous pressure were not modified by CNP.

4. Present findings show that centrally applied CNP modulates bile secretion in a dose-dependent fashion. CNP alkalinized bile and reduced bile acid-dependent flow without affecting bile acid-independent flow. The inhibitory response of CNP on bile secretion was not mediated by the autonomic nervous system. Present findings give further support to the role of CNP as the brain natriuretic peptide.

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REFERENCES

  • Anand-Srivastava, M. B., and Trachte, G. J. (1993). Atrial natriuretic factor receptors and signal transduction mechanisms. Pharmacol. Rev. 45:455–497.

    Google Scholar 

  • Balabaud, C., Noel, M., Beraud, C., and Dangoumau, J. (1975). Circadian rhythm of bile secretion in the rat. Experientia 31:1299–1303.

    Google Scholar 

  • Beckh, K., and Arnold, R. (1991). Regulation of bile secretion by sympathetic nerves in perfused rat liver. Am. J. Physiol. 261:G775–G780.

    Google Scholar 

  • Bianciotti, L.G., Elverdín, J.C., Vatta, M. S., and Fernández, B. E. (1996). Atrial natriuretic factor modifies the composition of induced-salivary secretion in the rat. Regul. Pept. 65: 139–143.

    Google Scholar 

  • Bianciotti, L.G., Vatta, M. S., Elverdín, J. C., Di Carlo, M. B., Negri,G., and Fernández, B. E. (1998). Atrial natriuretic factor-induced amylase output in the rat parotid gland is mediated by inositol phosphate pathway. Biochem. Biophys. Res. Commun. 247:123–128.

    Google Scholar 

  • Bianciotti, L. G., Vatta, M. S., Vescina, C., Trippodi, V., Sabbatini, M. E., and Fernández, B. E. (2001). Centrally applied atrial natriuretic factor diminishes bile secretion in the rat. Regul. Pept. 102:127–133.

    Google Scholar 

  • Bouscarel, B., Kroll, S. D., and Fromm, H. (1999). Signal transduction and hepatocellular bile acid transport: Cross talk between bile acids and second messengers. Gastroenterology 117:433–452.

    Google Scholar 

  • Bruusgaard, A. P. (1970). Quantitative determination of the major 3-hydroxy bile acids in biological materials after thin layer chromatographic separation. Clin. Chim. Acta 28:495–504.

    Google Scholar 

  • Chabot, J. G., Morel, G., Kopelman, H., Belle-Isles, M., and Heisler, S. (1987). Atrial natriuretic factor and exocrine pancreas: Autoradiographic localization of binding sites and ultrastructural evidence for internalization of endogenous ANF. Pancreas 2(4):404–413.

    Google Scholar 

  • Charles, C. J., Espiner, E. A., Richards, A. M., Nicholls, M. G., and Yandle, T. G. (1995). Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep. Am. J. Physiol. 268:R201–R207.

    Google Scholar 

  • Fernández, B. E., Bianciotti, L.G., Vatta, M. S., Dominguez, A. E., and Vescina,C. (1993). Atrial natriuretic factor modifies bile flow and composition in the rat. Regul. Pept. 143:177–184.

    Google Scholar 

  • Friman, S., Radberg, G., and Svanvik, J. (1990). Adrenergic influence on bile secretion—an experimental study. Acta Physiol. Scand. 140:287–293.

    Google Scholar 

  • Furuya, M. (1992). Structural requirements of C-type natriuretic peptide for elevation of cyclic GMP in cultured vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 183:964–969.

    Google Scholar 

  • Gademann, A., Puschel, G. P., and Jungermann, K. (1992). Nervous control of liver metabolism and hemodynamics. Eur. J. Biochem. 207:399–411.

    Google Scholar 

  • Gillis, R. A., Quest, J. A., Pagani, F. D., and Norman, W. P. (1989). Central centers in the central nervous system for regulating gastrointestinal motility. In Wood, J. D. (ed.), Handbook of Physiology. Section 6: The Gastrointestinal System, American Physiological Society, Bethesda, Washington, DC, pp. 621–683.

    Google Scholar 

  • Gower, W. R., Dietz, J. R., Vessely, D. L., Finley, C. L., Scholnick, K. A., Fabbri, P. J. Cooper, D. R., and Chalfant, C. E. (1994). Atrial natriuretic peptide gene expression in the gastrointestinal tract. Biochem. Biophys. Res. Commun. 202:562–570.

    Google Scholar 

  • Hagenbuch, B., Steiger, B., Foguet, M., Lubbert, H., and Meier, P. J. (1991). Functional expression, cloning and characterization of the hepatocyte NaC/bile acid cotransport system. Proc. Soc. Natl. Acad. Sci. U.S.A. 88:10629–10630.

    Google Scholar 

  • Janowski, M., Petrone, C., Tremblay, J., and Gutknowska, J. (1996). Natriuretic peptide system in the rat submaxillary glands. Regul. Pept. 62:53–61.

    Google Scholar 

  • Kojima, M., Minamino,N., Kangawa, K., and Matsuo,H. (1990). Cloning and sequence analysis of acDNA encoding a precursor for rat C-type natriuretic peptide (CNP). FEBS Lett. 276:209–213.

    Google Scholar 

  • Koller, K. J., and Goeddel, D. V. (1992). Molecular biology of the natriuretic peptides and their receptor. Circulation 86(4):1081–1088.

    Google Scholar 

  • Komatsu, Y., Nakao, K., Suga, S., Ogawa, Y., Mukoyama, M., Arai, H., Shirakami, G., Hosoda, K., Nakagama, O., Hama, N., Kishimoto, I., and Imura, H. (1991). C-type natriuretic peptide (CNP) in rats and humans. Endocrinology 129:1104–1106.

    Google Scholar 

  • Kullak-Ublick, G. A., Stieger, B., Hagenbuch, B., and Meier, P. J. (2000). Hepatic transport of bile salts. Semin. Liver Dis. 20(3):277–292.

    Google Scholar 

  • Langub, M.C., Jr., Dolgas, C. M., Watson, R. E., Jr., and Herman, J.P. (1995).The C-type natriuretic peptide receptor is the predominant natriuretic peptide receptor mRNA expressed in rat hypothalamus. J. Neuroendocrinol. 7:305–309.

    Google Scholar 

  • Masuda, M., Kanai, S., Miyasaka, K., and Funakoshi, A. (1995). Somatostatin inhibits pancreatic exocrine secretion centrally via sympathetic nerves in conscious rats. J. Auton. Nerv. Syst. 56:31–37.

    Google Scholar 

  • Matejka, M., Vescina, C., and Alayon, A. (1987). Micrométodo para la determinación de fosfolípidos en bilis humana. Acta Bioquim. Latinoamer. 21:351–355.

    Google Scholar 

  • Middendorff, R., Maronde, E., Paust, H.-J., Muller, D., Davidoff, M., and Olcese, J. (1996). Expression of C-type natriuretic peptide in the bovine pineal gland. J. Neurochem., 67:517–524.

    Google Scholar 

  • Nagain, C., Chariot, J., and Roce, C. (1993). Mechanism of neurotensin of external pancreatic secretion in the rat. Pancreas 8(3):346–353.

    Google Scholar 

  • Paxinos, E., and Watson, J. (1986). The Rat Brain Stereotaxic Coordinates. Academic Press, Sydney, Australia.

    Google Scholar 

  • Puyó, A. M., Vatta, M. S., Donoso, A. S., Bianciotti, L.G., and Fernández, B. E. (2000). Central natriuretic peptides regulation of peripheral atrial natriuretic factor release. Regul. Pept. 90:93–99.

    Google Scholar 

  • Rambotti, M.G., Giambanco, I., and Spreca, A. (1997). Detection of guanylate cyclasesAandBstimulated by natriuretic peptides in gastrointestinal tract of rat. Histochem. J. 29:117–126.

    Google Scholar 

  • Rodríguez-Fermepín, M., Vatta, M. S., Bianciotti, L.G., Wolovich, T., and Fernández, B. E. (2000). B-type and C-type natriuretic peptides modify norepinephrine uptake in discrete encephalic nuclei of the rat. Cell. Mol. Neurobiol. 20(6):763–771.

    Google Scholar 

  • Stepan, H., Leitner, E., Siems, W.-E., Maul, B., and Walther, T. (1999). RNA quantification of C-type natriuretic peptide in brain areas of rodents. Peptides 20:1243–1245.

    Google Scholar 

  • Sudoh, T., Minamino, N., Kangawa, K., and Matsuo, H. (1990). C-type natriuretic peptide (CNP): A new member of the natriuretic peptide family identified in porcine brain, Biochem. Biophys. Res. Commun. 168:863–870.

    Google Scholar 

  • Suga, S. I., Itoh, H., Komatsu, Y., Ogawa, Y., Hama, N., Yoshimasa, T., and Nakao, K. (1993). Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial 22 cells— evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells. Endocrinology 133:3038–3041.

    Google Scholar 

  • Suga, S., Nakao, K., Hosoda, K., Mukoyama, M., Ogawa,Y., Shirakami,G., Arai, H., Saito,Y., Kambayashi, Y., Inouye, K., and Imura, H. (1992). Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide. Endocrinology 130:229–239.

    Google Scholar 

  • Suzuki, E., Hirata, Y., Hayakawa, H., Omata, M., Kojima, H., Kangawa, K., Minamino, H., and Matsuo, H. (1993). Evidence for C-type natriuretic peptide production in rat kidney. Biochem. Biophys. Res. Commun. 192:532–538.

    Google Scholar 

  • Tietze, F. (1969). Enzymatic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal. Biochem. 27:502–522.

    Google Scholar 

  • Vatta, M. S., Presas, M. F., Bianciotti, L. G., Rodriguez-Fermepín, M., Ambros, R., and Fernández, B. E. (1997). B and C-types natriuretic peptides modify norepinephrine uptake and release in the rat adrenal medulla. Peptides 18(10):1483–1489.

    Google Scholar 

  • Vatta, M. S., Presas, M., Bianciotti, L. G., Zarrabeitia, V., and Fernández, B. E. (1996). B and C-types natriuretic peptides modulate norepinephrine uptake and release in the rat hypothalamus. Regul. Pept. 65:175–184.

    Google Scholar 

  • Vollmar, A. M., Paumgartner, G., and Gerbes, A. L. (1997). Differential gene expression of the three natriuretic peptides and natriuretic peptide receptors in human liver. Gut 40:145–150.

    Google Scholar 

  • Vorobioff, J., Bredfeldt, J. E., and Groszmann, J. (1983). Hyperdinamic circulation in portal hypertensive rat model of primary factor for maintenance of chronic portal hypertension. Am. J. Physiol. 244:G52–G57.

    Google Scholar 

  • Yoneda, M., Tamasawa, N., Takebe, K., Tamori, K., Yokohama, S., Sato, Y., Nakamura, K., Makino, I., and Tache, Y. (1995). Central neuropeptide Y enhances bile secretion through vagal and muscarinic but not nitric oxide pathway in rats. Peptides 16:727–732.

    Google Scholar 

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Sabbatini, M.E., Vatta, M.S., Vescina, C. et al. Bile Secretion Is Centrally Regulated by C-Type Natriuretic Peptide. Cell Mol Neurobiol 22, 755–770 (2002). https://doi.org/10.1023/A:1021813225723

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