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

Endocrinology. 2000 Sep;141(9):3210-24. doi: 10.1210/endo.141.9.7644.


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.

Publication types

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

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Autoradiography
  • Binding Sites
  • Blotting, Western
  • Colon / metabolism
  • Duodenum / metabolism
  • Gastrointestinal Hormones*
  • Guanylate Cyclase*
  • Intestinal Mucosa / metabolism*
  • Ligands
  • Luminescent Measurements
  • Male
  • Natriuretic Peptides
  • Peptides / metabolism*
  • Phosphodiesterase Inhibitors / pharmacology
  • Purinones / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Atrial Natriuretic Factor*
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology


  • Gastrointestinal Hormones
  • Ligands
  • Natriuretic Peptides
  • Peptides
  • Phosphodiesterase Inhibitors
  • Purinones
  • RNA, Messenger
  • Receptors, Cell Surface
  • guanylin
  • uroguanylin
  • Guanylate Cyclase
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor A
  • zaprinast
  • 1-Methyl-3-isobutylxanthine