1988 Fiscal Year Final Research Report Summary
Studies on intracellular mechanisms of intrinsic natriuretic substances
| Project/Area Number |
62570502
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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 |
内分泌・代謝学
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| Research Institution | University of Tokyo |
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Principal Investigator |
MATSUOKA Hiroaki The 2nd Department of Internal Medicine, University of Tokyo, 医学部(病), 講師 (20111544)
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| Co-Investigator(Kenkyū-buntansha) |
UEHARA Yoshio The 2nd Department of Internal Medicine, University of Tokyo, 医学部(病), 助手 (40184965)
GOTO Atsuo The 2nd Department of Internal Medicine, University of Tokyo, 医学部(病), 助手 (00150277)
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| Project Period (FY) |
1987 – 1988
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| Keywords | alpha-human atrial natriuretic peptide / endogenous digitalis-like factor / cGMP / aldosterone / adrenal glomerulosa cells / cultured vascular smooth muscle cells / A 10 cells / 細胞内Ca動態 |
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| Research Abstract |
To elucidate intracellular mechanisms of alpha-human atrial natriuretic peptide (ANP) and endogenous digitalis-like factor (EDF), we examined the effects of ANP and EDF on rat adrenal glomerulosa cells and aortic vascular smooth muscle cells. ANP inhibited aldosterone production in adrenal glomerulosa cells. This inhibitory effect of ANP on aldosterone production was associated with a marked increase in cGMP production. ANP also stimulated cGMP production in cultured vascular smooth muscle cells. These findings raise a possibility that cGMP is directly involved in the inhibitory effect on aldosterone production and vasodilating effect on vascular smooth muscle. However, sodium nitroprusside at concentrations of 10^<-5> - 10^<-3> M caused no significant changes in aldosterone production though it markedly increased cGMP production. Neither dibutyryl cGMP nor 8-bromo-cGMP affected aldosterone production. Furthermore, the aldosterone inhibitory effect of ANP was lost in the potssium free incubation medium, while the cGMP stimulating effect of ANP was not affected by adding potassium ion to the incubation medium at concentrations of 0 - 5 meq/1. We conclude that cGMP plays a minor role in the inhibitory effect of ANP on aldosterone production though ANP definitely stimulated intracellular cGMP levels.
EDF was purified from human urine by a combination of chromatographic procedures including reverse-phase high performance liquid chromatography. Effects of DEF on calcium ion fluxes and concentrationa in cultured rat vascular smooth muscle cells (A 10 cells) were examined using ^<45>Ca and fura 2. EDF enhanced net ^<45>Ca influx by 30 % and reduced ^<45>Ca efflux by 35 % in a 10 cells. Further, EDF increased intracellular free calcium ion in A 10 cells. These results indicate that EDF may modulate vascular tone by affecting intracellular calcium ion dynamics.
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