1987 Fiscal Year Final Research Report Summary
Role of phosphoinositide metabolism in mediation of the inhibitory effect of alpha1-adrenergic agonist on mouse thyroid.
| Project/Area Number |
61570111
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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 |
MUKAI Takamura Tokyo Women's Medical College, Prodessor, 教授 (50051446)
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| Co-Investigator(Kenkyū-buntansha) |
TSUKAHARA Fujiko Tokyo Women's Medical College, Instructor, 助手 (40119996)
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| Project Period (FY) |
1986 – 1987
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| Keywords | Inositol trisphosphate (IP_3) / Alpha_1-adrenoceptor / Mouse thyroid / ジグリセリド |
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| Research Abstract |
In mouse thyroids, norepinephrine (NE) inhibited the thyrotropin-induced release of thyroxine and increased phosphatidylinositol turnovel through acting on the alpha -adrenoceptors, suggesting that the inhibiroty effect of alpha_1 -Adrenergic agonists on thyroxine release in mediated by the degradation of polyphosphoinostitides. 1. To examine this possibility, we inverstigated the effects of adtenergic agonists on the production of (^3H)inositol phosphates in the mouse thyroid preincubated with (^3H)inositol for 3 h in vitro. NE (10^<-5> M) inctreased (^3H) inositol accumulation into inositol monophosphate, inositol bidphosphate, inositol trisphosphate (IP_3) of mouse thyrois linearly up to 30 min in the presence of lithium. The effect of NE was mimicked by phynylephrime but not by clonidine or isoproterenol, and was antagonized by prazosin but not by yohimbine or propranolo. These reults suggest that NE-induced production if inositol phosphates in mouse thyrois is mediated by alpha_1 -adtenoceptors. 2. 1,2 Diacylglycerol (DG) accumulated as early as 30 sec after addition of NE in thyroids preinucubated with (^3H) glycerol. NE-induced rise in DG production may probably be mediated through alpha,-adrenoceptors, because prazosin showed a tendency to dectease the NE-induced DG accumulation. 3. NEinduced a rather slow breakdown of phosphatidulinositol 4,8-bisphosphate (TPI) in (^<32>Pi)-labeled thyroids: a significant dectease in radioactivity of TPI fraction was seen after 5-10 min incubation with NE. 4. These results suggest that alpha_1 -adrenergic agonist inhibits the release of thyroid hormone from mouse thyroids most probably by inducing IP3 production, which in turn elevates the free cytosolic calcium levels. However, NE inctrases the production of DG from TPI, at least partly, therefore, DG may play some role in mediating the inhibitory alpha_1 effect in mouse thyroids through activation of protein kinase C.
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