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Intestinal Guanylate Cyclase-C mRNA Expression in Duodenum and Colon of Children
Mitchell B Cohen1, Benjamin D Gold2, Stavra A Xanthakos3
1Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
Insights
Guanylate cyclase-C (GC-C) mRNA expression is consistent in children over 6 months in the duodenum and over 12 months in the colon. These findings support the use of GC-C agonists for pediatric constipation.
Area of Science:
- Gastroenterology
- Pediatric Pharmacology
- Molecular Biology
Background:
- Guanylate cyclase-C (GC-C) agonists are utilized for chronic constipation and irritable bowel syndrome, with ongoing evaluation for pediatric applications.
- Previous research suggests potentially higher GC-C receptor density in younger children, which could influence treatment responses to GC-C agonists.
Purpose of the Study:
- To quantify duodenal and colonic GC-C mRNA expression in pediatric populations.
- To investigate the relationship between GC-C mRNA levels and age in children.
Main Methods:
- Mucosal biopsies were collected from pediatric subjects (6 months to 18 years) during endoscopy.
- GC-C mRNA expression was analyzed using quantitative polymerase chain reaction (qPCR).
- Regression analyses modeled the association between GC-C mRNA levels and patient age.
Main Results:
- Ninety-three evaluable samples showed mean relative GC-C mRNA expression of 2.36 in duodenal and 1.56 in colonic tissues.
- GC-C mRNA expression levels were comparable across different age groups in both duodenal and colonic samples.
- Colonic samples exhibited lower GC-C mRNA expression compared to duodenal samples across all age groups.
Conclusions:
- Consistent GC-C mRNA expression was observed in children over 6 months (duodenum) and 12 months (colon).
- Regional differences in GC-C mRNA expression (duodenum > colon) suggest variable receptor density.
- These findings provide reassurance for the continued investigation and use of GC-C agonists in pediatric patients.
Objectives:
Guanylate cyclase-C (GC-C) agonists, which increase intestinal secretion and accelerate transit, are used to treat chronic constipation and constipation-predominant irritable bowel syndrome and are being evaluated for pediatric use. Prior studies suggest GC-C receptor density may be higher in young children, potentially amplifying GC-C agonism with treatment implications. We aimed to quantitate duodenal and colonic GC-C mRNA expression in children.
Methods:
Mucosal biopsies were obtained from subjects aged 6 months to 18 years during clinically indicated upper, that is, esophago-gastro-duodenal, and/or colonic endoscopy. Tissue samples without histologic abnormalities were grouped by subject age (<24 months, 24 months to <6 years, 6 to <12 years, and 12 to <18 years) and analyzed for GC-C mRNA expression by qPCR. The relationship between GC-C mRNA levels and age was modeled using regression analyses.
Results:
Ninety-nine subjects underwent upper endoscopy/colonoscopy; 93 had evaluable samples. Mean relative GC-C mRNA expression was 2.36 (range 2.21-2.46) for duodenal samples and 1.56 (range 1.22-1.91) for colonic samples. Predicted and observed normalized GC-C mRNA expression in each region were comparable among age groups. Pooled expression by region demonstrated lower expression in colonic versus duodenal samples.
Conclusions:
Uniform levels of GC-C mRNA expression were detected in children aged >6 months in the duodenum and >12 months in the colon. Higher expression was observed in all age groups in duodenal versus colonic samples, indicating regional variability in GC-C receptor density. These data are reassuring for further studies of GC-C agonists in children.
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