Urine and plasma levels of uroguanylin and its molecular forms in renal diseases.
Uroguanylin activates the intestinal and possibly the renal guanylate cyclase C receptor, and stimulates Cl- secretion. We developed a sensitive radioimmunoassay (RIA) for human uroguanylin and measured its concentration in the urine and plasma. Twenty-four-hour urinary excretion of immunoreactive (ir-) uroguanylin for persons with a high-salt diet (10 g/day) was 137.8 +/- 14.4 pmol/day, significantly higher than that for persons with a low-salt diet (7 g/day, 95.1 +/- 16.3 pmol/day, P < 0.05). There were significantly positive correlations between the urinary excretion of ir-uroguanylin and Na+, Cl-, K+ or cyclic GMP (cGMP). We demonstrated the presence of messenger RNA of guanylate cyclase C in the medulla of human kidney. The concentration of plasma ir-uroguanylin significantly correlated with that of serum creatinine (r = 0.71, P < 0.001). Biologically active uroguanylin-16 accounted for 99% of the endogenous uroguanylin molecules in normal urine and 60% in plasma, the remainder being the 10 kDa precursor. The precursor content increased in the urine and plasma as the severity of renal impairment increased. These findings suggest that bioactive uroguanylin-16 is involved in the regulation of electrolyte homeostasis and that the kidney participates in the metabolism and excretion of uroguanylin.
Kinoshita
H
H
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Fujimoto
S
S
Nakazato
M
M
Yokota
N
N
Date
Y
Y
Yamaguchi
H
H
Hisanaga
S
S
Eto
T
T
D002940:Circadian Rhythm / Q000502:physiology; D003404:Creatinine / Q000097:blood; D006152:Cyclic GMP / Q000652:urine; D004039:Diet, Sodium-Restricted; D004573:Electrolytes / Q000652:urine; D005260:Female; D005768:Gastrointestinal Hormones; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D007536:Isomerism; D007674:Kidney Diseases / Q000097:blood* / Q000652:urine*; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D045265:Natriuretic Peptides; D009994:Osmolar Concentration; D010455:Peptides / Q000097:blood* / Q000652:urine*; D011498:Protein Precursors / Q000097:blood / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay
D004573:Electrolytes; D005768:Gastrointestinal Hormones; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D045265:Natriuretic Peptides; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; C095867:guanylin 16; C083435:preproguanylin; C084362:uroguanylin; D003404:Creatinine; D006162:Guanylate Cyclase; D006152:Cyclic GMP