Guanylyl Imidodiphosphate (lithium salt), a stable GTP analog, is a potent activator of adenylate cyclase[1]. Guanylyl Imidodiphosphate reduces the binding of agonist ligands (±)-[3H]epinephrine and (-)-[3H]norepinephrine to α-noradrenergic receptors in calf frontal cerebral cortex membranes, exhibiting IC50 values with 1-10μM[1]. Guanylyl Imidodiphosphate selectively and potently inhibits the high-affinity binding of the tritiated agonist with an IC50 value of 0.1µM[2-3].
In vitro, Guanylyl Imidodiphosphate and GTP significantly enhanced enzymatic activity of adenylate cyclase (EC4.6.1.1) in the renal plasma membranes of male Ranger strain chicks (Ross Poultry, Worcester)[4-5]. Guanylyl Imidodiphosphate, with EC50 achieved at 3.1μM concentration after 12min incubation, produced an 8.2-fold (720%) enhancement in enzymatic activity of adenylate cyclase relative to basal levels[5]. Guanylyl Imidodiphosphate demonstrated dose-dependent inhibition of nuclear membrane assembly in Xenopus egg extracts, at a concentration of 3mM, Guanylyl Imidodiphosphate completely blocked both vesicle fusion and nuclear envelope formation throughout the 160 minutes. When applied at 1mM concentration, Guanylyl Imidodiphosphate delayed the initiation of vesicle fusion by 80 minutes post-cytosol addition and significantly suppressed nuclear envelope expansion, reducing the growth rate of nuclear envelope by more than 6-fold[6].
References:
[1] U'Prichard D C, Snyder S H. Guanyl nucleotide influences on 3H-ligand binding to α-noradrenergic receptors in calf brain membranes[J]. Journal of Biological Chemistry, 1978, 253(10): 3444-3452.
[2] Mollereau C, Pascaud A, Baillat G, et al. 5′-Guanylylimidodiphosphate decreases affinity for agonists and apparent molecular size of a frog brain opioid receptor in digitonin solution[J]. Journal of Biological Chemistry, 1988, 263(34): 18003-18008.
[3] Roy C, LE BARS N C, JARD S. Vasopressin‐Sensitive Kidney Adenylate Cyclase: Differential Effects of Monovalent Ions on Stimulation by Fluoride, Vasopressin and Guanylyl 5′‐imidodiphosphate[J]. European Journal of Biochemistry, 1977, 78(2): 325-332.
[4] ABOU-ISSA H, REICHERT JR L E O E. Modulation of follicle-stimulating hormone-sensitive rat testicular adenylate cyclase activity by guanyl nucleotides[J]. Endocrinology, 1979, 104(1): 189-193.
[5] Hunt N H, Martin T J, Michelangeli V P, et al. Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney[J]. Journal of Endocrinology, 1976, 69(3): 401-412.
[6] Boman A L, Delannoy M R, Wilson K L. GTP hydrolysis is required for vesicle fusion during nuclear envelope assembly in vitro[J]. The Journal of cell biology, 1992, 116(2): 281-294.
Guanylyl Imidodiphosphate (lithium salt)是一种稳定的GTP类似物，是腺苷酸环化酶的有效激活剂。Guanylyl Imidodiphosphate能够减少激动剂配体（±）-[3H]肾上腺素和（-）-[3H]去甲肾上腺素与牛额叶大脑皮层膜中α-去甲肾上腺素受体的结合，IC50值范围为1-10μM[1]。Guanylyl Imidodiphosphate选择性且有效地抑制高亲和力的氚化激动剂结合，IC50值为0.1µM[2-3]。
在体外，Guanylyl Imidodiphosphate (lithium salt)和GTP显著增强了雄性Ranger品系雏鸡（Ross Poultry, Worcester）肾血浆膜中腺苷酸环化酶（EC4.6.1.1）的酶活性[4-5]。Guanylyl Imidodiphosphate在12分钟孵育后达到EC50的浓度为3.1μM，使酶活性相对于基础水平提高了8.2倍（720%)[5]。Guanylyl Imidodiphosphate在非洲爪蟾卵提取物中表现出剂量依赖性的核膜组装抑制作用，在3mM浓度下，Guanylyl Imidodiphosphate在160分钟内完全阻断了囊泡融合和核膜的形成。当浓度为1mM时，Guanylyl Imidodiphosphate将囊泡融合的起始时间延迟了80分钟，并显著抑制了核膜的扩张，将核膜生长速率降低了6倍以上[6]。