Project/Area Number |
09044326
|
Research Category |
Grant-in-Aid for international Scientific Research
|
Allocation Type | Single-year Grants |
Section | Joint Research |
Research Field |
内分泌・代謝学
|
Research Institution | Miyazaki Medical College |
Principal Investigator |
NAKAZATO Masamitsu Miyazaki Medical College, Third Department of Internal Medicine, Full time Lecturer, 医学部, 講師 (10180267)
|
Co-Investigator(Kenkyū-buntansha) |
GARBERS David L. University of Texas Southwestern Medical Center, Department of Pharmacology, Pro, 教授
MIYAZATO Mikiya National cardiovascular Center Research Institute, Department Biochemistry, Inve, 室員 (50291183)
KANGAWA Kenji National cardiovascular Center Research Institute, Department Biochemistry, Dire, 部長 (00112417)
MATSUKURA Shigeru Miyazaki Medical College, Third Department of Internal Medicine, Professor, 医学部, 教授 (70030939)
|
Project Period (FY) |
1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1997: ¥6,600,000 (Direct Cost: ¥6,600,000)
|
Keywords | uroguamylin / guanylin / cyclic GMP / guanylate cyclase / salt and water metabolism |
Research Abstract |
Uroguanylin, a 16-amino acid, is synthesized in the epithelia of stomack, intestine, kidney and lung. The peptide activates guanylyl cyclase C (GC-C) and causes Cl-secretion and inhibition of H2O and Na+ absorption. We clarified its tissue distribution, cellular source, structure-bioactivity relationship, and cDNA sequence. Twenty-four-hour urinary excretion of uroguanylin for persons with 10 g salt/day was significantly higher than that for persons with 7 g salt/day (137.8(]SY.+-。[)14.4 pmol/day vs 95.1(]SY.+-。[)16.3 pmol/day, p<0.05). Urinary uroguanylin excretion after 1 hr oral administration of 2% saline to normal subjects was increased 2.4 times the base. Intravenous administration of 2% saline did not change urinary uroguanylin excretion. Urinary uroguanylin excretion in rats kept with 8% NaCl food was 2.3 times higher than that of rats kept with 0.3% NaCl food. In the rat intestinal perfusion study, saline increased the release of uroguanylin into the intestinal lumen and mesenteric artery. GC-C mRNA was found in renal tubules as well as in the intestine. Uroguanylin may link the intestine and kidney in an endocrine pathway for the control of renal salt excretion.
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