| Project/Area Number |
03670111
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Tokyo Women's Medical College |
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Principal Investigator |
TAKAMURA Muraki Tokyo Women's Medical College professor, 医学部, 教授 (50051446)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAHARA Fujiko Tokyo Women's Medical college Instructor, 医学部, 助手 (40119996)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1991: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | atrial natriuretic peptide (ANP) / CNP / developmental pharmacology / guanylate cyclase / lung / kidney / 心房性ナトリウム利尿ペプチド / グアニル酸シクラーゼ / ANP受容体 / ノーザンブロット / 大動脈弛緩 / グアニル酸シクラ-ゼ |
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| Research Abstract |
To investigate the developmental changes of drug sensitivity, we studied changes in the effect of atrial natriuretic peptide (ANP) to increase the cGMP contents of aorta, kidney and lung slices obtained from neonate and adult (9 week old) rats. Human ANP(99-126)(0.1-1 uM) increased the slice cGMP content of aorta, kidney and lung. The ANP-stimulated fraction of cGMP content of lung slices increased with development, that of kidney slices decreased and no change in aorta slices. ANP stimulated the membrane-bound guanylate cyclase of the homogenate of these tissues. The developmental changes of ANP-stimulation of guanylate cyclase were similar to those of slice cGMP contents. CNP (ANP-B receptor specific) was as potent as ANP (ANP-A receptor specific) in stimulating membrane-bound guanylate cyclase in both kidney and lung homogenate. Developmental changes of CNP-stimulated guanylate cyclase were similar to those of ANP-stimulated activity, that is, increase in lung and decrease in kidney, suggesting that there is no differential changes between ANP-A and ANP-B receptor subtypes. No developmental changes were found in the relaxant effect of ANP on the ring preparation of thoracic aorta between 2 weeks old and 12 weeks old rats. We failed to show the ANP receptor mRNA by the Northern blot using bovine ANP receptor cDNA as a probe in kidney and lung, indicating the low level of expression of ANP receptor genes in these tissues. In conclusion, our study revealed the differential changes in ANP receptor abundance among tissues during development.
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