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Melanocortin receptors and δ-opioid receptor mediate opposite signalling actions of POMC-derived peptides in CATH.a cells

Authors

  • Frédérique René,

    1. Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, 21 rue René Descartes, 67084 Strasbourg Cedex, France,
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  • André Muller,

    1. Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, 21 rue René Descartes, 67084 Strasbourg Cedex, France,
    2. Clinique de la Douleur, Hospices Civils de Strasbourg, 6 rue de l'Hopital, 67000 Strasbourg, France,
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  • Emmanuel Jover,

    1. Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, 21 rue René Descartes, 67084 Strasbourg Cedex, France,
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  • Brigitte Kieffer,

    1. Laboratoire des Protéines et Récepteurs Membranaires, UPR CNRS 9050, Ecole supérieure de Biotechnologie, Parc de l'innovation, 67400 Illkirch, France
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  • Bernard Koch,

    1. Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, 21 rue René Descartes, 67084 Strasbourg Cedex, France,
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  • Jean-Philippe Loeffler

    1. Laboratoire de Neurophysiologie Cellulaire et Intégrée, UMR CNRS 7519, 21 rue René Descartes, 67084 Strasbourg Cedex, France,
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Correspondence: J.-P. Loeffler, as above. E-mail: Loeffler@neurochem.u-strasbg.fr

Abstract

The locus cœruleus is innervated by proopiomelanocortin (POMC)-derived peptide immunoreactive fibres. The biological effects of α melanocyte-stimulating hormone (αMSH) and β-endorphin on second messengers (cAMP, inositol phosphates) and gene transcription were studied in the locus cœruleus-derived cell line CATH.a.

 RT-PCR analysis revealed the presence of four MSH receptor subtypes (1, 3, 4 and 5). Activation of these receptors by diacetyl αMSH stimulated cAMP accumulation in a dose-dependent manner (EC50: 4 × 10–9m). Diacetyl αMSH stimulated transcription from reporter genes driven by the c-fos or tyrosine hydroxylase promoter. This effect was abolished when protein kinase A was inactivated with a dominant inhibitory mutant. RT-PCR analyses revealed the presence of δ-, but not μ-and κ-opioid receptor. Pharmacological analysis showed that β-endorphin (EC50: 2.5 × 10–8m), but not N-acetyl β-endorphin, antagonized the biological effect of diacetyl αMSH on cAMP production and gene transcription.

 Since N-acetylation regulates the biological activity of αMSH and β-endorphin in an opposite manner, we propose a model where the rate of secretion dictated by the bioelectric activity of the presynaptic neuron modulates POMC-derived peptide maturation and the resulting biological signal sensed by the postsynaptic plate.

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