Research Article| Volume 216, P63-71, January 2019

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Alterations in enteric calcitonin gene-related peptide in patients with colonic diverticular disease

CGRP in diverticular disease
Published:September 18, 2018DOI:


      • Colonic motility is known to be compromised in DD patients.
      • CGRP is important mediator of GI motility thus it was investigated in context of DD.
      • CGRP levels within the enteric plexuses are declined in symptomatic DD patients.
      • Longitudinal smooth muscles display elevated relaxant response to CGRP.
      • Alterations to CGRP might contribute to mobility impairment associated with DD.


      Diverticular disease (DD) is one of the most prevalent diseases of the large bowel. Lately, imbalance of neuro-muscular transmission has been recognized as a major etiological factor for DD. Neuronal calcitonin gene-related peptide (CGRP) is a potent gastrointestinal smooth muscle relaxant shown to have a widespread effect within the alimentary tract. Nevertheless, CGRPergic innervation of the enteric ganglia has never been considered in the context of motility impairment observed in DD patients.
      Changes in CGRP and calcitonin receptor-like receptor (CRLR) abundance within enteric ganglia were investigated in sigmoid samples from symptomatic and asymptomatic DD patients using quantitative fluorescence microscopy. CGRP effect on gastrointestinal smooth muscle was investigated using organ bath technique.
      We found CGRP levels within the enteric ganglia to be declined by up to 52% in symptomatic DD patients. Conversely, CRLR within the enteric ganglia was upregulated by 41% in symptomatic DD. Longitudinal smooth muscle displayed an elevated (+10.5%) relaxant effect to the exogenous application of CGRP in colonic strips from symptomatic DD patients. Samples from asymptomatic DD patients consistently showed intermediate values across different experiments.
      In conclusion, the present study demonstrates that CGRPergic signaling is subject to alteration in DD. Our results suggest that a hypersensitization mechanism to gradually decreasing levels of CGRP-IR nerve fibers takes place during DD progression. Alterations to CGRPergic signaling in DD disease may have implications for physiological abnormalities associated with colonic DD.


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      asymptomatic diverticular disease
      calcitonin gene-related peptide
      calcitonin receptor-like receptor
      diverticular disease
      enteric nervous system
      fluorescence intensity
      inner submucosal (Meissner's) plexus
      myenteric (Auerbach's) plexus
      nitric oxide
      neuronal nitric oxide synthase
      outer submucosal (Schabadasch's) plexus
      PGP 9.5
      protein gene-product 9.5 (pan-neuronal marker)
      receptor activity modifying protein 1
      symptomatic diverticular disease (diverticulitis)
      sodium nitroprusside
      vasoactive intestinal peptide