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Localization of receptors for calcitonin-gene-related peptide to intraganglionic laminar endings of the mouse esophagus: peripheral interaction between vagal and spinal afferents?

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Abstract

The calcitonin-gene-related peptide (CGRP) receptor is a heterodimer of calcitonin-receptor-like receptor (CLR) and receptor-activity-modifying protein 1 (RAMP1). Despite the importance of CGRP in regulating gastrointestinal functions, nothing is known about the distribution and function of CLR/RAMP1 in the esophagus, where up to 90 % of spinal afferent neurons contain CGRP. We detected CLR/RAMP1 in the mouse esophagus using immunofluorescence and confocal laser scanning microscopy and examined their relationship with neuronal elements of the myenteric plexus. Immunoreactivity for CLR and RAMP1 colocalized with VGLUT2-positive intraganglionic laminar endings (IGLEs), which were contacted by CGRP-positive varicose axons presumably of spinal afferent origin, typically at sites of CRL/RAMP1 immunoreactivity. This provides an anatomical basis for interaction between spinal afferent fibers and IGLEs. Immunoreactive CLR and RAMP1 also colocalized in myenteric neurons. Thus, CGRP-containing spinal afferents may interact with both vagal IGLEs and myenteric neurons in the mouse esophagus, possibly modulating motility reflexes and inflammatory hypersensitivity.

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Acknowledgments

The skillful technical assistance of Karin Löschner, Hedwig Symowski, Stefanie Link, Anita Hecht and Andrea Hilpert is gratefully acknowledged. This study was supported by Johannes und Frieda Marohn-Stiftung, Erlangen, and by the National Health and Medical Research Council (NWB), Australia.

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  1. Institute of Anatomy I, University of Erlangen-Nuremberg, Krankenhausstr. 9, 91054, Erlangen, Germany

    L. Horling, W. L. Neuhuber & M. Raab

  2. Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, VIC, 3052, Australia

    N. W. Bunnett

  3. Department of Pharmacology, University of Melbourne, Parkville, VIC, Australia

    N. W. Bunnett

  4. Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Universitätsstr. 17, 91054 Erlangen, Germany

    K. Messlinger

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  1. L. Horling
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Horling, L., Bunnett, N.W., Messlinger, K. et al. Localization of receptors for calcitonin-gene-related peptide to intraganglionic laminar endings of the mouse esophagus: peripheral interaction between vagal and spinal afferents?. Histochem Cell Biol 141, 321–335 (2014). https://doi.org/10.1007/s00418-013-1162-1

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