Highlights
- •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.
Abstract
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.
Keywords
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Abbreviations
ADDasymptomatic diverticular disease
CGRPcalcitonin gene-related peptide
CRLRcalcitonin receptor-like receptor
DDdiverticular disease
ENSenteric nervous system
FIfluorescence intensity
IRimmunoreactive
ISPinner submucosal (Meissner's) plexus
MPmyenteric (Auerbach's) plexus
NOnitric oxide
NOS1neuronal nitric oxide synthase
OSPouter submucosal (Schabadasch's) plexus
PGP 9.5protein gene-product 9.5 (pan-neuronal marker)
RAMP1receptor activity modifying protein 1
SDDsymptomatic diverticular disease (diverticulitis)
SNPsodium nitroprusside
TTXtetrodotoxin
VIPvasoactive intestinal peptide
Article info
Publication history
Published online: September 18, 2018
Accepted:
September 16,
2018
Received in revised form:
August 4,
2018
Received:
July 2,
2018
Identification
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