Expression of GC-C, a receptor-guanylate cyclase, and its endogenous ligands uroguanylin and guanylin along the rostrocaudal axis of the intestine.
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.
Qian
X
X
Department of Cell and Molecular Physiology, University of North Carolina, Chaptel Hill 27599-7545, USA.
Prabhakar
S
S
Nandi
A
A
Visweswariah
S S
SS
Goy
M F
MF
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D015153:Blotting, Western; D003106:Colon / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D005768:Gastrointestinal Hormones; D006162:Guanylate Cyclase; D007413:Intestinal Mucosa / Q000378:metabolism*; D008024:Ligands; D008163:Luminescent Measurements; D008297:Male; D045265:Natriuretic Peptides; D010455:Peptides / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D005768:Gastrointestinal Hormones; D008024:Ligands; D045265:Natriuretic Peptides; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C072685:guanylin; C084362:uroguanylin; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C011145:zaprinast; D015056:1-Methyl-3-isobutylxanthine