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

在小鼠甲状腺中，去甲肾上腺素(NE)通过作用于α-肾上腺素受体，抑制促甲状腺素的释放，增加磷脂酰肌醇的分泌，提示α_1-肾上腺素能激动剂对甲状腺激素释放的抑制作用是通过多磷肌肽的降解来实现的。1.为探讨这一可能性，我们研究了肾上腺素能激动剂对体外培养的小鼠甲状腺中(~3H)肌醇磷酸的生成的影响。在锂存在下，Ne(10^-lt；-5&gt；M)可线性增加小鼠甲状腺一磷酸肌醇、二磷酸肌醇和三磷酸肌醇(IP_3)中的(~3H)肌醇蓄积量。去甲肾上腺素的作用可被去甲肾上腺素所模拟，但不能被可乐定或异丙肾上腺素所模拟，可被哌唑嗪所拮抗，但不能被育亨宾或普萘洛尔所拮抗。这些结果表明，NE诱导的肌醇磷酸酶在小鼠甲状腺中的产生是由α_1受体介导的。2.1，2-二酰基甘油(DG)在加入NE 30秒后，在用~(3 H)甘油预输注的甲状腺中最早蓄积。去甲肾上腺素引起的DG生成增加可能是通过肾上腺素受体介导的，因为哌唑嗪有抑制去甲肾上腺素引起的DG积聚的趋势。3.NE诱导磷脂酰肌醇4，8-二磷酸(TPI)在(^&lt；32&gt；PI)标记的甲状腺中的降解相当缓慢：与NE孵育5-10分钟后，TPI组分的放射性显著下降。4.上述结果提示，α_1-肾上腺素能激动剂抑制小鼠甲状腺激素的释放可能是通过诱导IP3的产生，进而提高细胞内游离钙的水平。然而，NE至少部分地促进了TPI产生DG，因此DG可能通过激活蛋白激酶C而在介导小鼠甲状腺α_1抑制效应中起一定作用。

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.