title: Localization of receptors for calcitonin-gene-related peptide to intraganglionic laminar endings of the mouse esophagus: peripheral interaction between vagal and spinal afferents?
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.
authors.affiliation: Institute of Anatomy I, University of Erlangen-Nuremberg, Krankenhausstr. 9, 91054, Erlangen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Horling
authors.forename: N W
authors.initials: NW
authors.lastname: Bunnett
authors.forename: K
authors.initials: K
authors.lastname: Messlinger
authors.forename: W L
authors.initials: WL
authors.lastname: Neuhuber
authors.forename: M
authors.initials: M
authors.lastname: Raab
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics / Q000378:metabolism*; D004947:Esophagus / Q000294:innervation* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000378:metabolism; D058262:Receptor Activity-Modifying Protein 1 / Q000235:genetics / Q000378:metabolism*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D050599:Vesicular Glutamate Transport Protein 2 / Q000096:biosynthesis
chemical_list: D058286:Calcitonin Receptor-Like Protein; D058262:Receptor Activity-Modifying Protein 1; D018015:Receptors, Calcitonin Gene-Related Peptide; D050599:Vesicular Glutamate Transport Protein 2; D015740:Calcitonin Gene-Related Peptide