1998 Fiscal Year Final Research Report Summary
Analysis of guanylin family system using knock-out mouse
| Project/Area Number |
10044306
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
内分泌・代謝学
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
NAKAZATO Masamitsu Miyazaki Medical College, Third Department of Internal Medicine, Full time Lecturer, 医学部 (10180267)
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| Co-Investigator(Kenkyū-buntansha) |
柳沢 正史 テキサス大学, 薬理学, 教授
山口 秀樹 宮崎医科大学, 医学部, 助手 (10305097)
MIYAZATO Mikiya National cardiovascular Center Research Institute, Department Biochemistry, Inve, 生化学部, 室員 (50291183)
KANGAWA Kenji National cardiovascular Center Research Institute, Department Biochemistry, Dire, 生化学部, 部長 (00112417)
MATSUKURA Shigeru Miyazaki Medical College, Third Department of Internal Medicine, Professor, 医学部, 講師 (70030939)
GARBERS David L. University of Texas Southwestern Medical Center, Department of Pharmacology, Pro
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| Project Period (FY) |
1998
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| Keywords | uroguanylin / guanylin / cycle GMP / guanylate cyclase / salt and water metabolism |
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| Research Abstract |
Uroguanylin, a member of the guanylin peptide family, acts on guanylyl cyclase C (GC-C) to regulate intestinal and renal fluid and electrolyte transportthrough the second messenger, cyclic GMP.Using an antiserum raised against synthetic rat uroguanylin, we established a radioimmunoassay and identifiedthree endogenous molecular forms : a 15-amino acid uroguanylin, an 18-amino acid uroguanylin that is a monobasic processing product, and a 9.4-kDa prouroguanylin. Prouroguanylin is the major molecular form in these two tissues, whereas only 15-amino-acid uroguanylin is present in the urine.
Uroguanylin is present immunohistochemically in the enterochromaffin cells in the intestine, enterochromaffin-like cells in the stomach, B cells in thepancreatic islets, and tubular epithelial cells in the kidney by immunocytochemical methods using antisera for uroguanylin and prouroguanylin, as well as by hybridization cytochemistry. Uroguanylin has a widespread tissue distribution and is located in cel
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ls which function in an endocrine, paracrine and/or luminocrine (luminal secretion) fashion. The uroguanylin and guanylin genes are arranged in a tail-to-tail array in both species. The respective intergenic distances between the two genes in the human and mouse genomes are approximately 6.5 and 8 kb. The intergenic region between the human uroguanylin and guanylin genes has an Alu sequence and a (CA/FG)19 microsatellite sequence. These findings should help provide a better understandingof the regulatory mechanism of gene expression of the guanylin family peptides, as well as of the molecular mechanism of the evolution of this family.
Plasma uroguanylin levels were significantly higher in patients with heart failure than those in controls (6.7 fmol/ml vs 4.8 fmol/ml). Plasma uroguanylinconcentrations in the coronary sinus and anterior interventricular vein are higher than that in the aorta, suggesting cardiac secretion of uroguanylin into thecirculation. Uroguanylin may function in the regulation of fluid and electrolyte balance in cardiac failure. Less
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[Publications] Date Y, Nakazato M, Yamaguchi H, Kangawa K, Kinoshita Y, Chiba T, Ueta Y, Yamashita H, Matsukura S: "Enterochromaffin-like cell, a cellular source of uroguanylin in rat stomach." Endocrinology, in press.
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