1990 Fiscal Year Final Research Report Summary
Grant-in-Aid for Scientific Research (A)
| Project/Area Number |
63440042
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kyoto University |
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Principal Investigator |
IMURA H Kyoto University Faculty of Medicine, Professor, 医学部, 教授 (10025570)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAO. K Kyoto University Faculty of Medicine, Assistant Professor, 医学部, 講師 (00172263)
NAKAI Y Kyoto University Faculty of Medicine, Assistant Professor, 医学部, 講師 (10115892)
SEINO Y Kyoto University Faculty of Medicine, Associate professor, 医学部, 助教授 (40030986)
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| Project Period (FY) |
1988 – 1990
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| Keywords | ANP / BNP / CNP / POMC / Cytokines / Leumorphin / GIP / Motilin |
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| Research Abstract |
To elucidate the regulation of ANP gene expression, we studied ANP mRNA levels in rat and human heart. In normal rat and human, ANP mRNA was present predominantly in the atrium, whereas ventricular ANP mRNA levels were markedly increased in hypertensive rats with cardiac hypertrophy and in patients with congestive heart failure. We next studied on BNP, a new peptide of the same family. Our studies demonstrated that there are considerable species differences in the size and amino acid sequence among mammals. BNP mRNA was predominantly present in the ventricle, suggesting that BNP is the ventricular hormone. BNP gene expression is augmented in congestive heart failure. Both ANP and BNA have the central action. They inhibited water and salt intake, blood pressure rise, vasopression and ACTH release induced by angiotensin-II. CNP, another peptide of the natriuretic peptide family, is present in the brain but not in the heart.
We also studied the expression of proopiomelanocortin (POMC) gene. The 5'-flanking portion of the human POMC gene with the CAT gene as a reporter was introduced into cells and studied the expression. Cyclic AMP response element was identified. Glucocorticoid inhibition was seen only in AtT-20 cells, suggesting the involvement of some nuclear factors in the negative regulation of the POMC gene.
The third project in this series was the cloning of gastric inhibitory polypeptide and motilin cDNA and genes. The studies elucidated the amimo acid sequence of GIP and motilin precursors, their gene structures and their expression in man.
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