Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells.
Mechanism of cyclic GMP inhibition of inositol phosphate formation in rat aorta segments and cultured bovine aortic smooth muscle cells.
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DOI：
10.1016/s0021-9258(19)40008-2
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发表时间：
1990-01
期刊：
影响因子：
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通讯作者：
Masato Hirata;K. Kohse;C. Chang;T. Ikebe;Ferid Murad
中科院分区：
文献类型：
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作者：
Masato Hirata;K. Kohse;C. Chang;T. Ikebe;Ferid Murad
为了阐明环鸟苷酸抑制大鼠主动脉节段和培养的牛主动脉平滑肌细胞磷酸肌醇生成的机制，我们研究了培养的牛主动脉平滑肌细胞匀浆和膜制备物中磷酸肌醇水解和GT3活性。预处理的匀浆制剂与环GMP加ATP并不抑制[8-精氨酸，3 H]加压素（AVP）的结合，但导致AVP诱导的GT3激活的总抑制。用环GMP和ATP预处理还抑制在低浓度鸟苷5 '-（γ-硫代）三磷酸（GTP γ S）存在下由AVP诱导的肌醇磷酸的形成，或单独由高浓度GTP γ S诱导的肌醇磷酸的形成。然而，单独高浓度的Ca 2+的肌醇磷酸的形成没有被阻止。这些结果表明，环GMP抑制磷酸肌醇水解的能力是由于抑制鸟嘌呤核苷酸调节蛋白的活化，以及鸟嘌呤核苷酸调节蛋白和磷脂酶C之间的相互作用。虽然这种抑制的精确位点目前尚不清楚，但环GMP的抑制依赖于ATP的加入，并且可能需要磷酸化事件，因为腺苷酰亚氨基二磷酸不能替代ATP的需要。
In order to clarify the mechanism(s) by which cyclic GMP inhibits the generation of inositol phosphates in rat aorta segments and cultured bovine aortic smooth muscle cells, we studied phosphoinositide hydrolysis and GTPase activity in homogenates and membrane preparations of cultured bovine aortic smooth muscle cells. Pretreatment of homogenate preparations with cyclic GMP plus ATP did not inhibit [8-arginine, 3H] vasopressin (AVP) binding, but resulted in a total suppression of the AVP-induced GTPase activation. The pretreatment with cyclic GMP and ATP also inhibited the formation of inositol phosphates induced by AVP in the presence of low concentrations of guanosine 5'-(gamma-thio)triphosphate (GTP gamma S), or by high concentrations of GTP gamma S alone. However, the formation of inositol phosphates by high concentrations of Ca2+ alone was not blocked. These results suggest that the ability of cyclic GMP to inhibit phosphoinositide hydrolysis results from an inhibition of a guanine nucleotide regulatory protein activation, and the interaction between guanine nucleotide regulatory protein and phospholipase C. While the precise site of this inhibition is not presently known, the inhibition by cyclic GMP is dependent upon the addition of ATP and probably entails a phosphorylation event since adenylylimidodiphosphate can not substitute for the ATP requirement.