Disease relevance of guanylyl imidodiphosphate

• This was done by assessing N component activity in reconstitution assays that measured the capacity of luteal N to mediate, in cyc- S49 lymphoma membranes, stimulation of adenylyl cyclase independently by the guanine nucleotide guanylyl imidodiphosphate, by NaF, or by the lymphoma membrane beta-adrenergic receptor [1].
• Here we have investigated the possible involvement of pertussis toxin (PT)-sensitive guanosine-5'-triphosphate (GTP)-binding proteins (G-proteins) in ET-1-induced activation of these two signalling pathways in porcine coronary artery smooth muscle [2].
• Phosphorylation of glucose by a guanosine-5'-triphosphate (GTP)-dependent glucokinase in Fibrobacter succinogenes subsp. succinogenes S85 [3].
• Na(+)-Ca2+ exchange stimulated by 5' guanylyl imidodiphosphate [Gpp (NH) p] was decreased by 65.7% in late phase of sepsis but unaltered in early phase of sepsis [4].

High impact information on guanylyl imidodiphosphate

• To test this idea electrophysiologically, we have injected purified GTP-binding protein that was binding a hydrolysis-resistant analogue of GTP, guanylyl imidodiphosphate (p(NH)ppG), termed Gp(NH)ppG, as well as partially purified PDE, into toad rod outer segments while recording membrane voltage [5].
• The squid giant synapse was used to test the hypothesis that guanosine-5'-triphosphate (GTP)-binding proteins regulate the local distribution of synaptic vesicles within nerve terminals [6].
• Guanylyl imidodiphosphate [Gpp(NH)p] converted agonist binding sites on the receptor, from high-affinity to the low-affinity state, thus indicating that the cloned receptors couple to endogenous G-proteins [7].
• Polymerization of tubulin by Gmp(CH2)pp is neither prevented nor reversed by concentrations of calcium (2 mM) that can either prevent microtubule assembly or disrupt already formed microtubules if the nucleotide used is GTP or guanylyl imidodiphosphate [8].
• Biochemical analysis confirms that guanylyl-imidodiphosphate activates adenylate cyclase in Aplysia californica nervous tissue, without affecting phosphodiesterase activity [9].

Biological context of guanylyl imidodiphosphate

• In accord with their minimal dynamic instability, assembled HeLa cell microtubules displayed a slow treadmilling rate and a low guanosine-5'-triphosphate hydrolysis rate at steady state [10].
• Extracellular guanosine-5'-triphosphate modulates myogenesis via intermediate Ca(2+)-activated K+ currents in C2C12 mouse cells [11].
• Guanosine-5'-triphosphate (GTP; 100 microM) shifts the agonist competition curves to the right, increasing the IC50 values [12].
• The differential sensitivity to guanylyl-imidodiphosphate suggests the existence of at least two vasoactive intestinal peptide receptor subtypes in brain, with distinct regional distribution, and may reflect differential coupling to second messenger systems [13].
• We propose that the amino acid sequence encoded by this cDNA clone contains a tripartite guanosine-5'-triphosphate (GTP)-binding motif, GXXXSGKS/T, DXXG and T/NKXD, and a signature of the dynamin family, LPRG(S/K)GIVTR, which are conserved in all IFN-induced Mx proteins of vertebrates [14].

Anatomical context of guanylyl imidodiphosphate

• Choleragen-catalyzed inhibition of GTPase and [32P]ADP-ribosylation of the 39-kDa protein required guanylyl imidodiphosphate and did not occur in dark ROS membranes [15].
• The guanylyl imidodiphosphate-activated state of turkey erythrocyte cyclase can be reversed to the basal state by the simultaneous action of beta-agonists and GTP [16].
• By contrast, preincubation of sarcolemma with guanylyl imidodiphosphate stimulated the formation of an 'activated' form of the enzyme, which did not reveal increased hormonal sensitivity [17].
• BACKGROUND: Halothane is an effective bronchodilator and inhibits airway smooth muscle contraction in part by inhibiting intracellular signaling pathways activated by the M2 muscarinic receptor and its cognate inhibitory heterotrimeric guanosine-5'-triphosphate (GTP)-binding protein (G protein), Gi [18].
• Autoradiographic studies were performed in the presence and absence of 10 microM Gpp(NH)p. Binding in D2 containing regions, such as the caudate-putamen, was completely inhibited by guanylyl-imidodiphosphate although binding in D3 containing areas, such as the islands of Calleja, was unaffected [19].

Associations of guanylyl imidodiphosphate with other chemical compounds

• METHOD: Adenylyl cyclase activity stimulated by dopamine and by guanylyl-imidodiphosphate (to assess G protein and adenylyl cyclase coupling) was determined in the postmortem brain tissue of 16 methamphetamine users who had used the drug both recently and chronically (i.e., at least 1 year) as well as 21 matched comparison subjects [20].
• The receptor could be radiolabelled with [3H]-5-HT with a Kd value of 1.3 +/- 0.1 nM and a Bmax value of 3461 +/- 186 fmoles/mg protein and the radiolabelling was sensitive to the stable guanosine 5'-triphosphate (GTP) analogue guanylyl-imidodiphosphate (GMP-PNP) [21].
• BACKGROUND: This study investigated whether halothane affects the functional coupling between the beta2 adrenergic receptor and the alpha subunit of its cognate stimulatory heterotrimeric guanosine-5'-triphosphate (GTP)-binding protein (Galphas) [22].
• Our data indicate that guanosine-triphosphate (GTP) and guanyl-5'-yl imidodiphosphate (Gpp(NH)p) enhance the binding of 8-(4-[(([(2-amino-ethyl)amino]carbonyl) methyl)oxyl]phenyl)-1,3-dipropylxanthine ([3H]XAC) to adipocyte membranes in a dose-dependent manner, with EC50 values being 1.8 and 2.2 microM, respectively [23].
• Intact hepatocytes respond to extracellular ATP, adenosine-5'-O-(3-thiotriphosphate) (ATP gamma S), ADP and weakly to guanosine-5'-triphosphate (GTP), but not to other purine nucleotides (GDP or AMP) [24].

Gene context of guanylyl imidodiphosphate

• Assignment of a gene that determines erythrocytic guanosine-5'-triphosphate concentration (Gtpc) to mouse chromosome 9 [25].
• The Km values of the GAP domains compare well to the binding affinity to the guanylyl imidodiphosphate-bound Cdc42, suggesting a rapid equilibrium reaction mechanism [26].
• CCK-B receptor heterogeneity is suggested by the effect of the guanyl nucleotide analogue, guanylyl-imidodiphosphate (Gpp(NH)p), on [3H]SNF 8702 binding to CCK-B receptors in the cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)[27]
• AM infusion also upregulated the gene expression of guanosine-5'-triphosphate cyclohydrolase I and downregulated the expression of p22(phox), suggesting that AM increased the NOS coupling and bioavailability of NO [28].
• However, in the presence of edeine or guanylyl imidodiphosphate, both of which cause accumulation of 48 S initiation complexes, eIF-4E was detected in the 48 S region [29].

Analytical, diagnostic and therapeutic context of guanylyl imidodiphosphate

• We then studied the intrinsic dynamin GTPase mechanism by using a combination of fluorescence stopped-flow and HPLC methods using the fluorescent analogue of GTP, mantdGTP (2'-deoxy-3'-O-(N-methylanthraniloyl) guanosine-5'-triphosphate), under the same ionic strength conditions [30].

References