Guanine nucleotides stimulate production of inositol trisphosphate in rat cortical membranes.
Guanine nucleotides stimulate production of inositol trisphosphate in rat cortical membranes.
复制标题
鸟嘌呤核苷酸刺激大鼠皮质膜中肌醇三磷酸的产生。
DOI：
10.1042/bj2320799
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Crews,FT
中科院分区：
文献类型：
--
作者：
Gonzales,RA;Crews,FT
鸟苷5‘[β，γ-亚胺]三磷酸(GPP[NH]p)、鸟苷5’-[γ-硫代]-三磷酸(GTP-Gamma S)、GMP、GDP3和GTP可刺激大鼠大脑皮层膜上磷酸二酯酶对肌醇磷脂的水解。将100微米GPP[NH]p加入到预标记膜中，可使[~3H]肌醇磷酸根迅速累积(小于30 S)长达2分钟。GTP、S和GPP[NH]p对肌醇磷脂磷酸二酯酶有浓度依赖性的刺激作用，在100微米时最大刺激倍数为对照的2.5-3倍。GMP与非水解性类似物一样有效，但效力小得多(EC50 380微米)。GTP和GDP在100微米时对磷脂酶C有50%的刺激作用，而在较高浓度时对磷脂酶C有抑制作用。腺嘌呤核苷App[NH]p和三磷酸腺苷也有较小的兴奋作用(%和29%)。鸟嘌呤核苷酸对肌醇磷脂的刺激作用对肌醇磷脂的选择性高于对胆碱磷脂的作用。GPP[NH]p能刺激三磷酸肌醇、二磷酸肌醇和一磷酸肌醇的生成，说明肌醇是磷酸二酯酶的底物。EGTA(33微米)不能阻止鸟苷对肌醇解酶的刺激作用。钙单加可引起肌醇磷二酯酶的激活，激活范围为3~100微米，与GPP[NH]p的刺激相加。这些数据表明，鸟嘌呤核苷酸可能在调节大鼠皮质膜上肌醇磷脂磷酸二酯酶的活性中起到调节作用。
The guanine nucleotides guanosine 5′[beta, gamma-imido]triphosphate (Gpp[NH]p), guanosine 5′-[γ-thio]-triphosphate (GTP gamma S), GMP, GDP and GTP stimulated the hydrolysis of inositol phospholipids by a phosphodiesterase in rat cerebral cortical membranes. Addition of 100 microM-Gpp[NH]p to prelabelled membranes caused a rapid accumulation of [3H)inositol phosphates (less than 30 s) for up to 2 min. GTP gamma S and Gpp [NH]p caused a concentration-dependent stimulation of phosphoinositide phosphodiesterase with a maximal stimulation of 2.5-3-fold over control at concentrations of 100 microM. GMP was as effective as the nonhydrolysable analogues, but much less potent (EC50 380 microM). GTP and GDP caused a 50% stimulation of the phospholipase C at 100 microM and at higher concentrations were inhibitory. The adenine nucleotides App[NH]p and ATP also caused small stimulatory effects (64% and 29%). The guanine nucleotide stimulation of inositide hydrolysis in cortical membranes was selective for inositol phospholipids over choline-containing phospholipids. Gpp[NH]p stimulated the production of inositol trisphosphate and inositol bisphosphate as well as inositol monophosphate, indicating that phosphoinositides are substrates for the phosphodiesterase. EGTA (33 microM) did not prevent the guanine nucleotide stimulation of inositide hydrolysis. Calcium addition by itself caused inositide phosphodiesterase activation from 3 to 100 microM which was additive with the Gpp[NH]p stimulation. These data suggest that guanine nucleotides may play a regulatory role in the modulation of the activity of phosphoinositide phosphodiesterase in rat cortical membranes.