Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

BMC Gastroenterology

Research Article

Steen S Poulsen¹  Niels Bindslev²  Philip S Osbak³  Maria C Tilotta³  Nicolai Kaltoft³  Mark B Hansen⁴  Anne-Barbara Witte⁵ 

[1] Department of Anatomy B, Panum Institute, University of Copenhagen, Copenhagen, Denmark;Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark;Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark;Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark;AstraZeneca, Research & Development, Mölndal, Sweden;Department of Surgery K, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark;Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden;

关键词: Indomethacin;    Cystic Fibrosis Transmembrane Conductance Regulator;    Ouabain;    Bumetanide;    Short Circuit Current;   

DOI  :  10.1186/1471-230X-10-9

 received in 2009-06-03, accepted in 2010-01-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundThe pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect.MethodsPatients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM), various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology.ResultsBaseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027). Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH) did not differ significantly between the two groups. Histology was with normal findings in both groups.ConclusionsEpithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared to colonic mucosa from control patients. Stimulated epithelial electrogenic transport through individual prostanoid subtype receptors EP1, EP2, EP3, and EP4 is not significantly different between neoplasia diseased patients and controls. This indicates that increased indomethacin-sensitive mechanisms in colonic mucosa from neoplasia diseased patients are not related to differences in functional expression of EP receptor subtypes.

【 授权许可】

Unknown   
© Kaltoft et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.