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Differential signal transduction by five splice variants of the PACAP receptor

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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.

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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
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  2. Christian Waeber
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  3. Colette Pantaloni
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  4. Florian Holsboer
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  5. Joël Bockaert
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  6. Peter H. Seeburgt
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  7. Laurent Journot
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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

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

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