Guanine nucleotides mediate stimulatory and inhibitory effects on cerebral-cortical membrane phospholipase C activity.
Guanine nucleotides mediate stimulatory and inhibitory effects on cerebral-cortical membrane phospholipase C activity.
复制标题
鸟嘌呤核苷酸介导对大脑皮质膜磷脂酶 C 活性的刺激和抑制作用。
DOI：
10.1042/bj2610245
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Litosch,I
中科院分区：
文献类型：
--
作者：
Litosch,I
在大脑皮层细胞膜上，耐水解鸟嘌呤核苷酸对磷脂酶C的活性具有双重调节作用。纳米浓度的鸟苷5‘-[β-伽马亚胺]三磷酸(p[NH]ppg)或5’-[γ-硫代]鸟苷(S)对基础磷脂酶C活性有抑制作用，10 nM时最大抑制率为30%。当p[NH]ppg或GTP[S]浓度增加到10 nM以上时，对磷脂酶C活性的抑制作用被逆转，磷脂酶C活性开始被刺激。这些抑制作用可被100微米鸟苷5‘-[β-硫代]二磷酸阻断。GTP对磷脂酶C活性的刺激或抑制作用相对较弱。同样，三磷酸腺苷、5‘-[β-伽马亚胺]三磷酸和GDP也无效。鸟嘌呤核苷酸的双重效应的表达受镁离子浓度的影响。当镁离子浓度为0.3 mM时，p[NH]ppg作用的抑制成分和刺激成分均明显。当镁离子浓度为2.5 mM时，仅观察到p[NH]ppg刺激。百日咳毒素处理可阻断p[NH]ppg对磷脂酶C活性的抑制。这些结果表明，非水解性鸟嘌呤核苷酸对细胞膜磷脂酶C的活性既有促进作用，也有抑制作用。这些作用可能是通过不同的GTP结合蛋白介导的。
In cerebral-cortical membranes, hydrolysis-resistant guanine nucleotides exert a dual regulatory effect on phospholipase C activity. Nanomolar concentrations of guanosine 5′-[beta gamma-imido]triphosphate (p[NH]ppG) or guanosine 5′-[gamma-thio]triphosphate (GTP[S]) inhibited basal phospholipase C activity, with a maximum inhibition of 30% at 10 nM. Increasing the concentration of p[NH]ppG or GTP[S] to over 10 nM resulted in a reversal of the inhibitory effect and onset of stimulation of phospholipase C activity. These inhibitory effects were blocked by 100 microM-guanosine 5′-[beta-thio]diphosphate. GTP was relatively ineffective in producing either stimulation or inhibition of phospholipase C activity. Similarly, ATP, adenosine 5′-[beta gamma-imido]triphosphate and GDP were also ineffective. Expression of the dual effects of guanine nucleotides was affected by the Mg2+ concentration. At 0.3 mM-Mg2+, both the inhibitory and the stimulatory components of p[NH]ppG action were evident. At 2.5 mM-Mg2+, only p[NH]ppG stimulation was observed. Pertussis-toxin treatment blocked the p[NH]ppG-mediated inhibition of phospholipase C activity. These results demonstrate that non-hydrolysable guanine nucleotides exert both a stimulatory and an inhibitory effect on membrane phospholipase C activity. These effects may be mediated through distinct GTP-binding proteins.