Proguanylin secretion and the role of negative-feedback inhibition in a villous epithelial cell line.
The mechanisms of proguanylin synthesis and secretion in the intestine are incompletely understood. We designed an in vitro model to study proguanylin secretion in a model of intestinal villous epithelial cells. The C2/bbe1 cell line, a differentiated subclone of Caco-2 cells, was used to examine the direction of proguanylin secretion and the potential for feedback regulation via activators of the guanylyl cyclase C signal transduction pathway. When cells were grown on Transwell inserts, proguanylin was secreted into the apical and basolateral media, consistent with other models of intestinal guanylin secretion. Proguanylin synthesis and secretion were not decreased on activation of guanylyl cyclase C-mediated chloride secretion, implying a regulatory system other than negative-feedback inhibition. These data describe the use of C2/bbe1 cells as a model for proguanylin secretion in villous epithelial cells and demonstrate their potential use for the study of the regulatory mechanisms governing proguanylin synthesis and secretion.
Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. rudoj0@chmcc.org
Jeffrey A
JA
Rudolph
Jennifer A
JA
Hawkins
Mitchell B
MB
Cohen
D018938:Caco-2 Cells / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003584:Cytological Techniques / Q000295:instrumentation; D020895:Enterocytes / Q000502:physiology; D005246:Feedback; D005768:Gastrointestinal Hormones; D006162:Guanylate Cyclase / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D002712:Chlorides; D005768:Gastrointestinal Hormones; D007527:Isoenzymes; D011498:Protein Precursors; D012333:RNA, Messenger; C083435:preproguanylin; D006162:Guanylate Cyclase