Abstract
Parathyroid hormone (PTH) mobilises calcium in the hepatocyte, an effect which is abolished by verapamil and staurosporine. In our study parathyroid hormone was shown to act additively to dHGF in inducing hepatocyte DNA synthesis. It is also shown that PTH induced the production of inositol 1,4,5 trisphosphate (IP3) andc-fos expression at early times in culture. Co-incubation of PTH and dHGF with ac-fos antisense oligodeoxynucleotide inhibited hepatocyte DNA synthesis, indicating that the additive effect of PTH is correlated with the induction ofc-fos. H-89, a PKA specific inhibitor, inhibited the PTH effect on IP3 production as well as the PTH effect on hepatocyte DNA synthesis. Verapamil and staurosporine also inhibited the PTH effect in dHGF-induced DNA synthesis. Therefore it is suggested that PKA mediated at a great extent the co-stimulatory effects of PTH on hepatocyte proliferation via IP3 production.
Similar content being viewed by others
References
Chausmer, A. B., Sherman, S. S. and Wallach, S. (1972)Endocrinol 90:663–672.
Rixon, R. H., Isaacs, R. J. and Whitfield, J. F. (1989)J Cell Physiol 139:354–360.
Klin, M., Smogorzewski, M., Khilnani, H., Michnowska, M. and Massry, S. G. (1994)Am J Physiol 267:G754-G763.
Kano, J., Sugimoto, T., Kanatani, M., Kuroki, Y., Tsukamoto, T., Fukase, M. and Chihara, K. (1994)J Cell Physiol 161:358–366.
Cohen, P. (1988)Proc. R. Soc. London B234:115–144.
Michalopoulos, G. K. (1990)FASEB J. 4:176–187.
Fausto, N. and Webber, E. M. (1993)Crit. Rev. Eukaryot. Gene Expr. 3:117–135.
Etienne, P. L., Baffet, G., Desvergenes, B., Boisnard-Rissel, M., Glaise, D. and Guguen-Guillouzo, C. (1988)Oncogene Res. 3:255–262.
Michalopoulos, G. K. (1994) HGF and Liver Growth Regulation in: “Liver Carcinogenesis: The Molecular Pathways”. G. G. Skouteris (ed.), Springer Verlag H88, pp. 13–32.
Sikorska, M., Whitfield, J. F. and Rixon, R. H. (1983)J Cell Physiol 115:297–304.
Mine, T., Kojima, I. and Ogata, E. (1989)Biochem. J. 258:889–894.
Seglen, O. O. (1976)Meth. Cell Biol. 13:29–83.
Skouteris, G. G. and McMenamin, M. (1992)Biochem. J. 281:729–733.
Kapp, L. N., Brown, S. L. and Levecz, R. R. (1974)Biochim. Biophys. Acta 361:140–143.
Chomczynski, P. and Sacchi, N. (1987)Anal. Biochem. 162:156–159.
Shima, N., Tsuda, E., Goto, M., Yano, K., Hayasaka, H. and Higashio, K. (1994)Biochem. Biophys. Res. Commun. 200:808–815.
Kruijer, W., Skelly, H., Botteri, F., Van der Putten, H., Barber, J. R., Verma, I. M. and Leffert, H. L. (1986)J. Biol. Chem. 260:7929–7933.
Fabregat, I., Dejuan, C., Nakamura, T. and Benito, M. (1992)Biochem. Biophys. Res. Commun. 189:684–690.
Skouteris, G. G. and Kaser, M. R. (1992)J Cell Physiol 150:353–359.
Skouteris, G. G. and Schröder, C. H. (1995)Biochem. J., in press.
Abdul-Badi, A., Jueppner, H., Westerberg, D., Potts, J. T. and Segre, G. V. (1989)Endocrinol. 124:1107–1113.
Tamure, T., Sakamoto, H. and Filburn, C. R. (1989)Biochem. Biophys. Res. Commun. 159:1352–1358.
Stojceva-Taneva, O., Fadda, G. Z., Smogorzewski, M. and Massry, S. G. (1993)Nephron 64:592–599.
Skouteris, G. G. and Kaser, M. R. (1991)Biochem. Biophys. Res. Commun. 178:1240–1246.
Osada, S., Nakashima, S., Saji, S., Nakamura, T. and Nozawa, Y. (1992)FEBS Lett. 297:271–274.
Zuscik, M. J., Puzas, J. E., Rosier, R. N., Gunter, K. K. and Gunter, T. E. (1994)Arch. Biochem. Biophys. 315:352–361.
Ohtsuki, M. and Massague, J. (1992)Mol. Cell Biol. 12:261–265.
Klin, M., Smogorzewski, M., Khilnani, H., Michnowska, M. and Massry, S. G. (1994)Am. J. Physiol. 267:G754–763.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Skouteris, G.G. Parathyroid hormone co-stimulation of hepatocyte proliferation is sensitive to protein kinase A and calcium channel inhibitors. Biosci Rep 16, 343–350 (1996). https://doi.org/10.1007/BF01855017
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01855017