Disease relevance of 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate

• VASP mutated (Ser/Thr to Ala) at all three of its established phosphorylation sites (vesicular stomatitis virus-tagged VASP-AAA mutant) was not phosphorylated by cGK I and was resistant to detaching from HUVEC focal adhesions in response to 8-pCPT-cGMP [1].
• 5. In endothelium-denuded strips, the relaxation induced by 8-para-chlorophenyl thio-guanosine-3', 5'-cyclic monophosphate (8-pCPT-cGMP) on the STA2 contraction was significantly less for pre-eclampsia [2].
• After 3 h of anoxia, cardiomyocytes were transiently protected against apoptosis induced by NO, but not by 8-pCPT-cGMP or YC-1 (8.9 +/- 0.7% or 13.4 +/- 2.4% apoptotic cells) [3].

High impact information on 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate

• Furthermore, STa, guanylin, and 8-pCPT-cGMP stimulation of electrogenic anion secretion and inhibition of Na(+) absorption in vitro were markedly reduced in the small intestine from cGK II -/- mice but not in proximal colon [4].
• As cGMP levels also may be affected by IBMX, resistant cells were treated with 8-pCPT-cGMP, resulting in the complete restoration of GC-box binding, luciferase reporter activity, and RFC mRNA levels [5].
• Incubation of umbilical vein ECs with 8-pCPT-cGMP did not cause VASP phosphorylation and had no effect on the thrombin-induced increases in cytoplasmic Ca2+ and endothelial permeability.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• Activation of cGMP-dependent protein kinase by 8-PCPT-cGMP decreased the accumulation of cytoplasmic Ca2+ in aortic endothelial cells and hence reduced the thrombin-induced increase in permeability [7].
• Bath application of 8-parachlorophenylthio-cyclic GMP (8-pcpt-cGMP) has been shown to increase the number of action potentials per burst in the Aplysia neuron R15 [8].

Biological context of 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate

• Apoptosis induction was mimicked by incubation of cardiomyocytes with 8-pCPT-cGMP (100 microM, 9.6 +/- 0.6% apoptotic cells) or YC-1 (75 microM, 14.6 +/- 2.8% apoptotic cells), a direct activator of soluble guanylyl cyclase [3].
• Activators of PKA (Sp-cAMPS) and PKG (8-pCPT-cGMP) increase EPSP amplitude, mimicking the effects of DF2 [9].
• Use of the cGMP analog 8-pCPT-cGMP minimized problems associated with limited cell permeation or cGMP hydrolysis [10].

Anatomical context of 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate

• KT5823 enhanced 8-pCPT-cGMP-stimulated VASP phosphorylation in platelets and did not inhibit forskolin-stimulated VASP phosphorylation in either platelets or mesangial cells [11].
• RESULTS: SNP, SIN-1, or 8-pCPT-cGMP increased Isc with a change in the potential difference that became more negative toward the nonpigmented epithelium (aqueous) side [12].
• In beta-escin-permeabilized arteries, equivalent reductions in basal and agonist-enhanced myofilament calcium sensitivity were produced by much lower 8-pCPT-cGMP concentrations in fetal (172 and 61 microM, respectively) than in adult (410 and 231 microM, respectively) basilars [13].
• In muscle cells overexpressing the active phosphorylation site-deficient mutant Rho(A188), MLC(20) phosphorylation was partly inhibited by SNP, VIP, cBIMPS, and 8-pCPT-cGMP, suggesting the existence of an independent inhibitory mechanism downstream of RhoA [14].
• In the first series of experiments we studied the effects of the cGMP analogues 8-pCPT-cGMP (0.001-100 nM), Rp-8-pCPT-cGMPS (0. 01-100 nM), Rp-8-Br-cGMPS (0.01-100 nM), and Rp-8-Br-PET-cGMPS (0.01-100 nM) on the release of progesterone, insulin-like growth factor I (IGF-I) and oxytocin by cultured porcine granulosa cells [15].

Associations of 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate with other chemical compounds

• Quantitatively, 8-pCPT-cGMP was more effective than 8-Br-cGMP in inducing phosphorylation of the 46/50 kDa vasodilator-stimulated phosphoprotein, a major substrate of cGMP-PK in intact platelets [16].

Gene context of 8-(4-Chlorophenylthio)guanosine-3'-5'-cyclic monophosphate

• However, direct application of cADPR or 8-pCPT-cGMP stimulated migration of CD38(-) cells [17].
• In contrast H89, an inhibitor of both PKA and cGK, clearly inhibited 8-pCPT-cGMP and forskolin-stimulated VASP phosphorylation in the two cell types [11].
• In GC-A -/- hearts, the immediate contractile responses to CNP and 8-pCPT-cGMP were significantly enhanced [18].
• Furthermore, cGMP analogues such as 8-pCPT-cGMP, which selectively activates PKG but does not inhibit PDE3, had no effect on NF-kappaB-mediated transcription [19].
• The ANP effects, but not the 8-pCPT-cGMP effects, reversed after 3 h of treatment [1].

References