Tiger G, Björklund P E, Cowburn R F, Garlind A, O'Neill C, Wiehager B, Fowler C J
Department of Pharmacology, University of Umea, Sweden.
Eur J Pharmacol. 1990 Jan 23;188(1):51-62. doi: 10.1016/0922-4106(90)90247-u.
It has been suggested that K+, Li+ and Fl- affect the function of G proteins coupled to signal transducing enzymes. Lithium, at concentrations which were found to reduce forskolin-stimulated adenylate cyclase activity, was without effect on either membrane [3H]phosphatidylinositol-4,5-bisphosphate ([3H]PIP2) hydrolysis measured in the absence or presence of 5'-guanylyl-imidodiphosphate (Gpp(NH)p), or (at greater than or equal to 2.3 mM Li+) upon the stimulation of rat cerebral cortical inositol phospholipid breakdown by either carbachol, noradrenaline or NaF measured at either 6 or 18 mM K+. The increase in assay [K+] greatly enhanced the inositol phospholipid response to carbachol but not to NaF. The inhibitory effect of carbachol upon forskolin-stimulated adenylate cyclase was not affected by raising the [K+] from 6 to 18 mM. At 6 mM K+ (both in the absence and presence of 15 microM AlCl3), the effects of carbachol and NaF upon inositol phospholipid breakdown were essentially additive, whereas at 18 mM K+, the breakdown response to carbachol (antagonised by pirenzepine with a pA2 value of 7.6) was similar in the absence and presence of NaF. It is concluded that in the rat cerebral cortex: (a) Li+ does not affect the function of either the phosphoinositide-specific phospholipase C enzyme itself or the Gp coupled to this enzyme; (b) the difference between the additivity between NaF and carbachol seen at different assay [K+] may reflect the K(+)-dependent changes in the tetrodotoxin-resistant and tetrodotoxin-sensitive pathways of carbachol stimulation of inositol phospholipid breakdown reported by Gurwitz and Sokolovsky (1987, Biochemistry 26, 633); and (c) the effect of K+ on muscarinic receptor-coupled inositol phospholipid breakdown is not found for muscarinic receptors inhibitorily coupled to adenylate cyclase. Evidence is also presented to suggest that NaF affects the dephosphorylation of the formed [3H]inositol polyphosphates.
有人提出，K⁺、Li⁺和Fl⁻会影响与信号转导酶偶联的G蛋白的功能。锂在能降低福斯可林刺激的腺苷酸环化酶活性的浓度下，对在不存在或存在5'-鸟苷酰亚胺二磷酸（Gpp(NH)p）的情况下所测定的膜[³H]磷脂酰肌醇-4,5-二磷酸（[³H]PIP₂）水解均无影响，或者（在Li⁺浓度大于或等于2.3 mM时）对在6 mM或18 mM K⁺条件下由卡巴胆碱、去甲肾上腺素或NaF刺激大鼠大脑皮质肌醇磷脂分解也无影响。测定中[K⁺]的增加极大地增强了肌醇磷脂对卡巴胆碱的反应，但对NaF的反应没有增强。卡巴胆碱对福斯可林刺激的腺苷酸环化酶的抑制作用不受[K⁺]从6 mM升高到18 mM的影响。在6 mM K⁺时（无论是否存在15 μM AlCl₃），卡巴胆碱和NaF对肌醇磷脂分解的作用基本是相加的，而在18 mM K⁺时，在不存在和存在NaF的情况下，对卡巴胆碱的分解反应（被哌仑西平拮抗，pA₂值为7.6）相似。得出的结论是，在大鼠大脑皮质中：（a）Li⁺不影响磷酸肌醇特异性磷脂酶C酶本身或与其偶联的Gp的功能；（b）在不同测定[K⁺]下NaF和卡巴胆碱之间相加性的差异可能反映了Gurwitz和Sokolovsky（1987年，《生物化学》26卷，633页）报道的卡巴胆碱刺激肌醇磷脂分解的河豚毒素抗性和河豚毒素敏感性途径中K⁺依赖性变化；（c）对于与腺苷酸环化酶抑制性偶联的毒蕈碱受体，未发现K⁺对毒蕈碱受体偶联的肌醇磷脂分解有影响。还提供了证据表明NaF会影响所形成的[³H]肌醇多磷酸的去磷酸化。
Zotero 插件