10965892

pubmed:Citation

9

Members of the receptor-guanylate cyclase (rGC) family possess an intracellular catalytic domain that is regulated by an extracellular receptor domain. GC-C, an intestinally expressed rGC, was initially cloned by homology as an orphan receptor. The search for its ligands has yielded three candidates: STa (a bacterial toxin that causes traveler's diarrhea) and the endogenous peptides uroguanylin and guanylin. Here, by performing Northern and Western blots, and by measuring [125I]STa binding and STa-dependent elevation of cGMP levels, we investigate whether the distribution of GC-C matches that of its endogenous ligands in the rat intestine. We establish that 1) uroguanylin is essentially restricted to small bowel; 2) guanylin is very low in proximal small bowel, increasing to prominent levels in distal small bowel and throughout colon; 3) GC-C messenger RNA and STa-binding sites are uniformly expressed throughout the intestine; and 4) GC-C-mediated cGMP synthesis peaks at the proximal and distal extremes of the intestine (duodenum and colon), but is nearly absent in the middle (ileum). These observations suggest that GC-C's activity may be posttranslationally regulated, demonstrate that the distribution of GC-C is appropriate to mediate the actions of both uroguanylin and guanylin, and help to refine current hypotheses about the physiological role(s) of these peptides.

eng

AIM

MEDLINE

0013-7227

Print

NLM

3210-24

pubmed-meshheading:10965892-1-Methyl-3-isobutylxanthine, pubmed-meshheading:10965892-Animals, pubmed-meshheading:10965892-Autoradiography, pubmed-meshheading:10965892-Binding Sites, pubmed-meshheading:10965892-Blotting, Western, pubmed-meshheading:10965892-Colon, pubmed-meshheading:10965892-Duodenum, pubmed-meshheading:10965892-Gastrointestinal Hormones, pubmed-meshheading:10965892-Guanylate Cyclase, pubmed-meshheading:10965892-Intestines, pubmed-meshheading:10965892-Ligands, pubmed-meshheading:10965892-Luminescent Measurements, pubmed-meshheading:10965892-Male, pubmed-meshheading:10965892-Natriuretic Peptides, pubmed-meshheading:10965892-Peptides, pubmed-meshheading:10965892-Phosphodiesterase Inhibitors, pubmed-meshheading:10965892-Purinones, pubmed-meshheading:10965892-RNA, Messenger, pubmed-meshheading:10965892-Rats, pubmed-meshheading:10965892-Rats, Sprague-Dawley, pubmed-meshheading:10965892-Receptors, Atrial Natriuretic Factor, pubmed-meshheading:10965892-Receptors, Cell Surface

Expression of GC-C, a receptor-guanylate cyclase, and its endogenous ligands uroguanylin and guanylin along the rostrocaudal axis of the intestine.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't