Role of phosphoinositide metabolism in mediation of the inhibitory effect of alpha1-adrenergic agonist on mouse thyroid.

Research Project

Project/Area Number	61570111
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	General pharmacology
Research Institution	Tokyo Women's Medical College
Principal Investigator	MUKAI Takamura Tokyo Women's Medical College, Prodessor, 教授 (50051446)
Co-Investigator(Kenkyū-buntansha)	TSUKAHARA Fujiko Tokyo Women's Medical College, Instructor, 助手 (40119996)
Project Period (FY)	1986 – 1987
Project Status	Completed (Fiscal Year 1987)
Budget Amount *help	¥2,000,000 (Direct Cost: ¥2,000,000) Fiscal Year 1987: ¥200,000 (Direct Cost: ¥200,000) Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords	Inositol trisphosphate (IP_3) / Alpha_1-adrenoceptor / Mouse thyroid / ジグリセリド / 【α_1】アドレナリン受容体 / イノシトールリン酸
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.