Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct;56(10):2223-2233.
doi: 10.1002/mc.22675. Epub 2017 Jun 15.

Acetylcholine-related proteins in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia

Morten Matthiesen Bach Damm  1 , Thorbjørn Søren Rønn Jensen  1 , Badar Mahmood  1 , Morten Lundh  2 , Steen Seier Poulsen  3 , Niels Bindslev  3 , Mark Berner Hansen  1   4
Affiliations

Acetylcholine-related proteins in non-neoplastic appearing colonic mucosa from patients with colorectal neoplasia

Morten Matthiesen Bach Damm et al. Mol Carcinog. 2017 Oct.

Abstract

The pathogenesis of colorectal neoplasia (CRN) has been associated with altered non-neuronal acetylcholine (ACh) metabolism. The aim of this study was to characterize expression, function, and cellular location of ACh-related proteins in biopsies obtained from endoscopic normal-appearing sigmoid colon in patients with and without CRN. Messenger-RNA (mRNA) levels of 17 ACh-related proteins were quantified by rt-qPCR. Functional responses to ACh, measured as electrogenic transepithelial short circuit current (SCC), were recorded using the Ussing chamber technique. Finally, cellular localization of choline transporter-like proteins (CTLs) and butyryl-cholinesterase enzyme (BChE) was determined by immunohistochemistry. mRNA expression of CTL1 and CTL4 was increased in patients with CRN (P = 0.002 and P = 0.04, respectively). In functional experiments, baseline SCC was increased in CRN patients. ACh induced rapid biphasic changes in SCC. An initial decreasing phase was observed in the minority of CRN patients versus the majority of controls (25% vs 69%, respectively, P = 0.031). For the second increasing phase of SCC, data indicated ACh-activation of two receptors. For both parts of the biphasic response, the half maximal effective concentration and maximal responses showed no difference between patient groups. Immunohistochemistry demonstrated CTL1, 3 and 4 and BChE to be localized to colonic crypt cells. We conclude that CRN is associated with increased expression of CTL1 and CTL4, augmented basal prostaglandin-dependent secretion, and altered functional channel response to ACh in human endoscopic normal-appearing colonic mucosa. The immunohistochemical findings support CTL1, CTL3, CTL4, and BChE to be involved in non-neuronal mucosal ACh metabolism.

Keywords: acetylcholine; choline transporter-like protein; colon cancer; human.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

MeSH terms

LinkOut - more resources