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NPY Receptor Subtypes and Their Signal Transduction

  • Chapter
Neuropeptide Y and Related Peptides

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 162))

Abstract

The neuropeptide Y family acts through five cloned G protein coupled receptors (Y1, Y2, Y4, Y5, y6), all of which bind two or more of the endogenous peptides. At least three subtypes (Y1, Y2 and Y5) may signal as homodimers, whose formation is independent of the presence of agonist or G protein heterotrimers. All the Y receptors display the full complement of pertussis-toxin sensitive Gi/o signalling pathways (mediated by α or βγ subunits) in a suitable cell context, including the inhibition of cAMP formation, intracellular Ca2+ mobilization and modulation of Ca2+ and K+ channels. However recent studies have highlighted emerging differences in the desensitization and cellular trafficking of each subtype. Signalling of the Y1 receptor is regulated by phosphorylation and palmitoylation at key C-terminal motifs, and on agonist stimulation this subtype rapidly associates with the inhibitory protein, β-arrestin 2. In contrast the interaction of the Y2 receptor with β-arrestin 2 is much less pronounced, consistent with its reduced ability to undergo clathrin-mediated internalization compared to Y1 and Y4 subtypes. This observation may have additional consequences for the spatial and temporal organization of longer-term Y receptor signals, since β-arrestins have a wider role as scaffolds for protein kinase cascades. However current evidence suggests that Y1, Y2, Y4 and Y5 subtypes are all able to couple to mitogen activated protein kinase pathways, and as a consequence influence the control of gene expression and cell fate.

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Authors and Affiliations

  1. Centre for Neuroscience Research, King’s College London, Hodgkin Building, Guy’s Campus, London, SE1 1UL, UK

    N. D. Holliday & H. M. Cox

  2. Department of Pharmacology and Pharmacotherapy, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    M. C. Michel

Authors
  1. N. D. Holliday
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  2. M. C. Michel
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  3. H. M. Cox
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Editors and Affiliations

  1. Afd. Farmacologie & Farmacotherapie, Academisch Medisch Centrum, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

    Martin C. Michel

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© 2004 Springer-Verlag Berlin Heidelberg

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Holliday, N.D., Michel, M.C., Cox, H.M. (2004). NPY Receptor Subtypes and Their Signal Transduction. In: Michel, M.C. (eds) Neuropeptide Y and Related Peptides. Handbook of Experimental Pharmacology, vol 162. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18764-3_3

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  • DOI: https://doi.org/10.1007/978-3-642-18764-3_3

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62282-3

  • Online ISBN: 978-3-642-18764-3

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