Uroguanylin, an intestinal natriuretic peptide, is delivered to the kidney as an unprocessed propeptide.
Orally delivered salt stimulates renal salt excretion more effectively than does iv delivered salt. Although the mechanisms that underlie this "postprandial natriuresis" are poorly understood, the peptide uroguanylin (UGn) is thought to be a key mediator. However, the lack of selective assays for UGn gene products has hindered rigorous testing of this hypothesis. Using peptide-specific assays, we now report surprisingly little UGn in rat intestine or plasma. In contrast, prouroguanylin (proUGn), the presumed-inactive precursor of UGn, is plentiful (at least 40 times more abundant than UGn) in both intestine and plasma. The intestine is the likely source of the circulating proUGn because: 1) the proUGn portal to systemic ratio is approximately two under normal conditions, and 2) systemic proUGn levels decrease rapidly after intestinal resection. Together, these data suggest that proUGn itself is actively involved in enterorenal signaling. This is strongly supported by our observation that iv infusion of proUGn at a physiological concentration produces a long-lasting renal natriuresis, whereas previously reported natriuretic effects of UGn have required supraphysiological concentrations. Thus, our data point to proUGn as an endocrine (i.e. circulating) mediator of postprandial natriuresis, and suggest that the propeptide is secreted intact from the intestine into the circulation and processed to an active form at an extravascular site.
Moss
Nicholas G
NG
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Fellner
Robert C
RC
Qian
Xun
X
Yu
Sharon J
SJ
Li
Zhiping
Z
Nakazato
Masamitsu
M
Goy
Michael F
MF
D000818:Animals; D005768:Gastrointestinal Hormones / Q000097:blood / Q000378:metabolism; D007422:Intestines / Q000737:chemistry; D007668:Kidney / Q000378:metabolism*; D008297:Male; D045283:Natriuretic Agents / Q000097:blood / Q000378:metabolism; D045265:Natriuretic Peptides / Q000097:blood / Q000378:metabolism*; D011498:Protein Precursors / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014020:Tissue Extracts / Q000737:chemistry
D005768:Gastrointestinal Hormones; D045283:Natriuretic Agents; D045265:Natriuretic Peptides; D011498:Protein Precursors; D014020:Tissue Extracts; C097400:prouroguanylin; C084362:uroguanylin; D012964:Sodium