Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Differential signal transduction by five splice variants of the PACAP receptor

Nature volume 365, pages 170–175 (1993)Cite this article

Abstract

THE two forms of pituitary adenylyl cyclase-activating polypeptide (PACAP-27 and -38) are neuropeptides of the secretin/glucagon/ vasoactive intestinal polypeptide/growth-hormone-releasing hor-mone family and regulate hormone release from the pituitary and adrenal gland1–3. They may also be involved in spermatogenesis4, and PACAP-38 potently stimulates neuritogenesis and survival of cultured rat sympathetic neuroblast5,6 and promotes neurite out-growth of PC-12 cells7. The PACAP type-I receptor (found in hypothalamus, brain stem, pituitary, adrenal gland and testes), specific for PACAP, is positively coupled to adenylyl cyclase and phospholipase C. The recently cloned type II receptor does not discriminate between PACAP and vasoactive intestinal polypeptide and is coupled to only adenylyl cyclase8. Here we have used a new expression cloning strategy, based on the induction of a reporter gene by cyclic AMP, to isolate a complementary DNA encoding the type-I PACAP receptor. On transfection of this cDNA, both PACAP-27 and -38 stimulate adenylyl cyclase with similar EC50 values (50% effective concentration, 0.1–0.4 nM), whereas only PACAP-38 stimulates phospholipase C with high potency (EC50 = 15 nM). Four other splice variants were isolated with insertions at the C-terminal end of the third intracellular loop. Expression of these cDNAs revealed altered patterns of adenylyl cyclase and phospholipase C stimulation, suggesting a novel mechanism for fine tuning of signal transduction.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Arimura, A. Regul. Peptides 37, 287–303 (1992).

    CAS  Google Scholar 

  2. Minkes, R. K. et al. Am. J. Physiol. 263, H1659–H1669 (1992).

    CAS  PubMed  Google Scholar 

  3. Miyata, A. et al. Biochem. biophys. Res. Commun. 164, 567–574 (1989).

    Article  CAS  Google Scholar 

  4. Gottschall, P. E., Tatsuno, I., Miyata, A. & Arimura, A. Endocrinology 127, 272–277 (1990).

    Article  CAS  Google Scholar 

  5. DiCicco-Bloom, E. & Deutsch, P. J. Regul. Peptides 37, 319 (1992).

    Article  Google Scholar 

  6. Pincus, D. W., DiCicco-Bloom, E. M. & Black, I. B. Nature 343, 564–567 (1990).

    Article  ADS  CAS  Google Scholar 

  7. Deutsch, P. J. & Sun, Y. J. biol. Chem. 267, 5108–5113 (1992).

    CAS  PubMed  Google Scholar 

  8. Ishihara, T., Shigemoto, R., Mori, K., Takahashi, K. & Nagata, S. Neuron 8, 811–819 (1992).

    Article  CAS  Google Scholar 

  9. Savarese, T. M. & Fraser, C. M. Biochem. J. 283, 1–19 (1992).

    Article  CAS  Google Scholar 

  10. Ishihara, T. et al. EMBO J. 10, 1635–1641 (1991).

    Article  CAS  Google Scholar 

  11. Jelinek, L. J. et al. Science 259, 1614–1616 (1993).

    Article  ADS  CAS  Google Scholar 

  12. Mayo, K. E. Molec. Endocr. 6, 1734–1744 (1992).

    CAS  PubMed  Google Scholar 

  13. Lin, C., Lin, S.-C., Chang, C.-P. & Rosenfeld, M. G. Nature 360, 765–768 (1992).

    Article  ADS  CAS  Google Scholar 

  14. Gaylinn, B. D. et al. Molec. Endocr. 7, 77–84 (1993).

    CAS  PubMed  Google Scholar 

  15. Mount, S. M. Nucleic Acids. Res. 10, 459–472 (1982).

    Article  CAS  Google Scholar 

  16. Giros, B. et al. Nature 342, 923–926 (1989).

    Article  ADS  CAS  Google Scholar 

  17. Monsma, F. J., McVittie, L. D., Gerfen, C. R., Mahan, L. C. & Sibley, D. R. Nature 342, 926–929 (1989).

    Article  ADS  CAS  Google Scholar 

  18. Dal Toso, R. et al. EMBO J. 8, 4025–4034 (1989).

    Article  CAS  Google Scholar 

  19. Tanabe, Y., Masu, M., Ishii, T., Shigemoto, R. & Nakanishi, S. Neuron 8, 169–179 (1992).

    Article  CAS  Google Scholar 

  20. Pin, J.-P., Waeber, C., Prezeau, L., Bockaert, J. & Heinemann, S. F. Proc. natn. Head. Sci. U.S.A. 89, 10331–10335 (1992).

    Article  ADS  CAS  Google Scholar 

  21. Lechleiter, J. et al. EMBO J. 9, 4381–4390 (1990).

    Article  CAS  Google Scholar 

  22. Lechleiter, J., Girard, S., Clapham, D. & Peralta, E. Nature 350, 505–508 (1991).

    Article  ADS  CAS  Google Scholar 

  23. Gottschall, P. E., Tatsuno, I. & Arimura, A. FASEB J. 5, 194–199 (1991).

    Article  CAS  Google Scholar 

  24. Cauvin, A. et al. Regul. Peptides 35, 161–173 (1991).

    Article  CAS  Google Scholar 

  25. Koch, B. & Lutz-Bucher, B. Regul. Peptides 38, 45–53 (1992).

    Article  CAS  Google Scholar 

  26. Kosugi, S. et al. J. biol. Chem. 267, 24153–24156 (1992).

    CAS  PubMed  Google Scholar 

  27. Schall, T. J. et al. Cell 61, 361–370 (1990).

    Article  CAS  Google Scholar 

  28. Spengler, D., Rupprecht, R., Phi-Van, L. & Holsboer, F. Molec. Endocr. 6, 1931–1941 (1992).

    CAS  PubMed  Google Scholar 

  29. Kozak, M. Nucleic Acids Res. 15, 8125–8148 (1987).

    Article  CAS  Google Scholar 

  30. Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  31. Salomon, J., Londos, C. & Rodbell, M. Analyt. Biochem. 58, 541–548 (1974).

    Article  CAS  Google Scholar 

  32. Colson, P. et al. Am. J. Physiol. 263, E1054–E1062 (1992).

    CAS  PubMed  Google Scholar 

  33. Mengot, G. et al. Molec. Brain Res. 10, 185–191 (1991).

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. CNRS-UPR 9023, Mécanismes moléculaires des communications cellulaires, CCIPE, rue de la cardonille, F-34094, Montpellier, Cedex 05, France

    Dietmar Spongier, Christian Waeber, Colette Pantaloni, Joël Bockaert & Laurent Journot

  2. Laboratory of Molecular Neuroendocrinology, University of Heidelberg, ZMBH, D-6900, Heidelberg, 1, Germany

    Dietmar Spongier, Peter H. Seeburgt & Laurent Journot

  3. Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Clinical Institute, D-8000, Munich, 40, Germany

    Dietmar Spongier & Florian Holsboer

Authors
  1. Dietmar Spongier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christian Waeber
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Colette Pantaloni
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Florian Holsboer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joël Bockaert
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Peter H. Seeburgt
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Laurent Journot
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spongier, D., Waeber, C., Pantaloni, C. et al. Differential signal transduction by five splice variants of the PACAP receptor. Nature 365, 170–175 (1993). https://doi.org/10.1038/365170a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/365170a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing