Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms coupled to adenosine A(1)- and histamine H(3)-receptors have been examined in the presynaptic inhibition of acetylcholine (ACh) release from the guinea pig ileum. Electrically evoked twitch contractions were used as a measure of neuronal ACh release. A(1)- and H(3)-receptors were activated by adenosine and R-(alpha)-methylhistamine (RAMH), respectively. The neuroinhibitory effect of adenosine and RAMH was augmented in the presence of the N-type Ca(2+) channel blocker, omega-conotoxin GVIA but unaffected by the L-type Ca(2+) channel blocker, nifedipine. The irreversible adenylyl cyclase inhibitor, MDL-12330A, potentiated the action of both adenosine and RAMH. Conversely, neither agonist was affected by the cAMP phosphodiesterase III and IV inhibitors, SKF-95654 and Ro-20-1724, respectively, or the cAMP antagonist, (R(p))-adenosine 3',5'-cyclic monophosphorothioate triethylamine. The neuromodulatory effect of adenosine, only, was potentiated by the cGMP phosphodiesterase V inhibitors, SKF-96231 and 1,3-dimethyl-6-(2-propoxy-5-methanesulfonylamidophenyl)- pyrazolo[3, 4-d]pyrimidin-4-(5H)-one but was unmodified by the cGMP analog, 8-bromo-cGMP or the guanylyl cyclase inhibitors, N-methylhydroxylamine and 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxaline-1-one (ODQ). N-Methylhydroxylamine reduced, and ODQ potentiated, the inhibitory action of H(3)-receptor activation, but 8-bromo-cGMP was without effect. The study suggests that presynaptic A(1)- and H(3)-receptors inhibit cholinergic neurotransmission in the guinea pig ileum by limiting the availability of intraneuronal Ca(2+) via inhibition of N-type Ca(2+) channels. The balance of evidence does not support the involvement of the adenylyl cyclase/cAMP or guanylyl cyclase/cGMP systems.
...
PMID:Signaling mechanisms coupled to presynaptic A(1)- and H(3)-receptors in the inhibition of cholinergic contractile responses of the guinea pig ileum. 1104 95

Short chain fatty acids (SCFA) stimulate colonic Na+ absorption and inhibit cAMP and cGMP-mediated Cl- secretion. It is uncertain whether SCFA have equivalent effects on absorption and whether SCFA inhibition of Cl- secretion involves effects on mucosal enzymes. Unidirectional Na+ fluxes were measured across stripped colonic segments in the Ussing chamber. Enzyme activity was measured in cell fractions of scraped colonic mucosa. Mucosal 50 mM acetate, propionate, butyrate and poorly metabolized isobutyrate stimulated proximal colon Na+ absorption equally (300%). Neither 2-bromo-octanoate, an inhibitor of beta-oxidation, nor carbonic anhydrase inhibition affected this stimulation. All SCFA except acetate stimulated distal colon Na+ absorption 200%. Only one SCFA affected proximal colon cGMP phosphodiesterase (PDE) (18% inhibition by 50 mM butyrate). All SCFA at 50 mM stimulated distal colon cAMP PDE (24-43%) and decreased forskolin-stimulated mucosal cAMP content. None of the SCFA affected forskolin-stimulated adenylyl cyclase in distal colon or ST(a)-stimulated guanylyl cyclase in proximal colon. Na+-K+-ATPase in distal colon was inhibited 23-51% by the SCFA at 50 mM. We conclude that all SCFA (except acetate in distal colon) stimulate colonic Na+ absorption equally, and the mechanism does not involve mucosal SCFA metabolism or carbonic anhydrase. SCFA inhibition of cAMP-mediated secretion may involve SCFA stimulation of PDE and inhibition of Na+-K+-ATPase.
...
PMID:Effects of short chain fatty acids on colonic Na+ absorption and enzyme activity. 1122 95

To clarify the contribution of intracellular Ca(2+) concentration ([Ca(2+)](i))-dependent and -independent signaling mechanisms in arteriolar smooth muscle (aSM) to modulation of arteriolar myogenic tone by nitric oxide (NO), released in response to increases in intraluminal flow from the endothelium, changes in aSM [Ca(2+)](i) and diameter of isolated rat gracilis muscle arterioles (pretreated with indomethacin) were studied by fluorescent videomicroscopy. At an intraluminal pressure of 80 mmHg, [Ca(2+)](i) significantly increased and myogenic tone developed in response to elevations of extracellular Ca(2+) concentration. The Ca(2+) channel inhibitor nimodipine substantially decreased [Ca(2+)](i) and completely inhibited myogenic tone. Dilations to intraluminal flow (that were inhibited by N(omega)-nitro-L-arginine methyl ester) or dilations to the NO donor S-nitroso-N-acetyl-DL-penicillamine (that were inhibited by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) were not accompanied by substantial decreases in aSM [Ca(2+)](i). 8-Bromoguanosine cGMP and the cGMP-specific phosphodiesterase inhibitor zaprinast significantly dilated arterioles yet elicited only minimal decreases in [Ca(2+)](i). Thus flow-induced endothelial release of NO elicits relaxation of arteriolar smooth muscle by a cGMP-dependent decrease of the Ca(2+) sensitivity of the contractile apparatus without substantial changes in the pressure-induced level of [Ca(2+)](i).
...
PMID:Selected contribution: NO released to flow reduces myogenic tone of skeletal muscle arterioles by decreasing smooth muscle Ca(2+) sensitivity. 1140 72

Cyclic GMP plays a key role in retinal phototransduction and its photoreceptor concentration is precisely controlled by the cooperative action of cGMP phosphodiesterase (PDE) and retinal guanylyl cyclase (retGC). However, studies of the relationship between these two systems have focused only on a Ca(2+)-mediated, indirect connection. Using a retinal "regulator of G-protein signaling" (RGS9-1) and its fragments, we show that the N-terminus of RGS9-1 inhibits retGC activity. We also indicate that the GGL domain and/or the RGS domain function as an internal suppressor against the N-terminus, suggesting that proteins bound to these domains regulate the inhibitory activity of the N-terminus. Direct interaction of retGC with RGS9-1 and its N-terminus is also proved by immunoprecipitation and an overlay technique. Since RGS9-1 also controls the lifetime of transducin-activated PDE through regulating GTPase activity of transducin, this study strongly suggests that RGS9-1 mediates the direct interaction between PDE and retGC systems, and that this ingenious mechanism plays an important role in tuning of cGMP concentration in photoreceptors.
...
PMID:Inhibition of retinal guanylyl cyclase by the RGS9-1 N-terminus. 1148 1

Partial sequencing of cDNA libraries to generate expressed sequence tags (ESTs) is an effective means of gene discovery, generation of molecular markers and characterization of transcription patterns. We have constructed an EST-database of the scaly green flagellate Scherffelia dubia (Chlorophyta) containing 361 sequences. cDNAs were obtained from interphase cells and from cells regenerating flagella. Analysis of the ESTs identified 138 EST-groups with significant similarity to known sequences. 134 EST-groups showed no significant similarity to any sequences in the databases. Most of the ESTs with similarity to known proteins are associated with typical interphase cell functions of a photosynthetic plant cell: assimilation of nutrients and biosynthesis of proteins. Others are related to the activation of the secretory pathway or the biogenesis of scales (e.g. kdo-synthase). Comparison of S. dubia ESTs with the genome of Arabidopsis thaliana and the EST database of Chlamydomonas reinhardtii revealed that S. dubia ESTs with similarity to known proteins were more similar to sequences in C. reinhardtii than to those of A. thaliana. Additionally, ESTs for guanylyl cyclase and cGMP phosphodiesterase are present in the two flagellates, but so far these gene products have not been found in embryophytes.
...
PMID:Analysis of expressed sequence tags (ESTs) from the scaly green flagellate Scherffelia dubia Pascher emend. Melkonian et Preisig. 1154 37

These studies report on the activation and induction of cGMP-dependent protein kinase (PKG) by exisulind and analogs and test the hypothesis that PKG is involved in the induction of apoptosis in colon tumor cells. Exisulind and analogs are proapoptotic drugs developed as inhibitors of cGMP phosphodiesterase gene families 5 and 2 that have been shown to sustain increased cGMP in SW480 and HT29 cells. At concentrations that induced apoptosis, both exisulind and CP461 increased PKG activity in SW480 cell supernatants. PKG activation was dose-dependent and sustained. Activation of PKG by exisulind and analogs was also seen in the colon tumor cell lines HT29, T84, and HCT116. The guanylyl cyclase activators YC-1 and guanylin increased PKG activity secondary to increased cellular cGMP and induced apoptosis in colon tumor cells. Exisulind and CP461 had no direct effect on purified PKG activity or on basal and stimulated PKG activity from cell supernatants. An additional effect of exisulind after 8 h of drug treatment was a dose-dependent increase of PKG Ibeta protein expression. beta-Catenin, a potential new substrate for PKG, whose regulation influences apoptosis, was phosphorylated by PKG in vitro. 32P-labeled cells treated with exisulind showed increased phosphorylation of beta-catenin. These data indicate that exisulind and analogs activate and induce PKG, resulting in increased phosphorylation of beta-catenin and enhanced apoptosis to promote colon tumor cell death.
...
PMID:Cyclic GMP-dependent protein kinase activation and induction by exisulind and CP461 in colon tumor cells. 1160 70

The regulation of cGMP-specific phosphodiesterase (PDE) 5 and soluble guanylate cyclase (GC) by cGMP- and cAMP-dependent protein kinases (PKG and PKA respectively) was examined in gastric smooth muscle. The NO donor, sodium nitroprusside (SNP), stimulated PDE5 phosphorylation and activity, which was blocked by the selective PKG inhibitor, KT5823, resulting in an elevation of cGMP levels. Activation of PKA either directly by Sp-5,6-dichloro-1-beta-d-ribofuranosyl benzimidazole 3',5'-cyclic monophosphothioate, or via isoproterenol- and forskolin-dependent increase in cAMP, also caused an increase in PDE5 phosphorylation and activity, but only in the presence of cGMP; consistent with the dependence of PDE5 phosphorylation and activity on cGMP binding to allosteric sites in the regulatory domain of PDE5. The selective PKA inhibitors, myristoylated protein kinase inhibitor and H-89, blocked the increase in PDE5 phosphorylation and activity induced by PKA. SNP also stimulated soluble GC phosphorylation and activity. KT5823 abolished phosphorylation and augmented soluble GC activity, implying feedback inhibition of soluble GC by PKG-dependent phosphorylation. Phosphorylation by PKG was direct and could be induced in vitro. Activation of PKA had no effect on soluble GC. Thus cGMP levels are regulated by PKG- and PKA-dependent activation of PDE5 and PKG-specific inhibition of soluble GC.
...
PMID:Activation of phosphodiesterase 5 and inhibition of guanylate cyclase by cGMP-dependent protein kinase in smooth muscle. 1169 8

Plateau potentials are prolonged membrane depolarizations that are observed in hippocampal pyramidal neurons when spiking and Ca(2+) entry occur in combination with muscarinic receptor activation. In this study, we used whole-cell voltage clamping to study the current underlying the plateau potential and to determine the cellular signaling pathways contributing to this current. When combined with muscarinic stimulation, depolarizing command potentials that evoked Ca(2+) influx elicited a prolonged tail current (I(tail)) that had an extrapolated reversal potential of -20 mV. I(tail) was not observed when intracellular Ca(2+) levels were chelated with 10 mm intracellular BAPTA, and I(tail) was reversibly depressed in low external sodium. When I(tail) was evoked at intervals >3 min, current amplitudes were stable for up to 1 hr. However, at shorter intervals, I(tail) was refractory, with a time constant of recovery of 43.5 sec. The inhibitors of soluble guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and 6-anilino-5,8-quinolinequinone depressed I(tail) and zaprinast, which blocks cGMP-specific phosphodiesterase, enhanced I(tail), suggesting that a component of I(tail) was activated by cGMP. The inhibitors of cyclic nucleotide-gated (CNG) channels l-cis-diltiazem and 2',4'-dichlorobenzamil reversibly depressed I(tail). However, protein kinase G inhibition had no effect. Therefore, these results indicate that a component of I(tail) is attributable to activation of CNG channels. We conclude that Ca(2+) influx when combined with muscarinic receptor activation activates soluble guanylate cyclase and increases cGMP levels. The increased cGMP activates CNG channels and leads to prolonged depolarization. The cation conductance of the CNG channel contributes to the prolonged depolarization of the plateau potential.
...
PMID:Cyclic nucleotide-gated channels contribute to the cholinergic plateau potential in hippocampal CA1 pyramidal neurons. 1169 82

Many lines of evidence show that membranes contain microdomains, "lipid rafts", that are different from the rest of the membrane in specific lipid and protein composition. In several biological systems, they were shown to be necessary for trafficking and signal transduction. Here, we investigate if lipid rafts have a role in the regulation of the G protein-mediated pathway underlying vertebrate phototransduction. Photoreceptor membranes contain detergent-resistant membrane (DRM) rafts. Rhodopsin and cGMP phosphodiesterase are found in raft and nonraft portions of the membrane; guanylate cyclase is found exclusively in the raft. Distribution of these proteins does not change in the light or dark. In contrast, the G protein transducin, the RGS9-1-Gbeta5L complex, and the p44 isoform of arrestin undergo dramatic translocation to the raft upon illumination. Phosphorylation of RGS9-1 occurs exclusively in the raft. GTPgammaS or pertussis toxin prevent the light-mediated translocation of transducin and RGS9-1, whereas AlF(minus sign)(4) causes both proteins to move to the raft in the dark. This shows that the Galphat-RGS9-1-Gbeta5L complex has the highest affinity to rafts in the transition state of the GTPase. GTPgammaS binds to transducin at a significantly slower rate in the raft, indicating that this translocation results in a reduced rhodopsin-transducin coupling. Thus, an external signal can rearrange components of a G protein pathway in specific domains of the cell membrane, changing its signaling properties. These findings could reveal a novel mechanism utilized by the cells for regulation of G protein-mediated signal transduction.
...
PMID:Signal-dependent translocation of transducin, RGS9-1-Gbeta5L complex, and arrestin to detergent-resistant membrane rafts in photoreceptors. 1188 95

Cyclic GMP plays a key role in retinal phototransduction and its photoreceptor concentration is precisely controlled by the cooperative action of cGMP phosphodiesterase (PDE) and retinal guanylyl cyclase (retGC). However, studies of the relationship between these two systems have focused only on a Ca2+-mediated, indirect connection. This article summarizes our studies strongly suggesting that RGS9-1 is directly involved in the cooperative action of PDE and retGC, and that this ingenious mechanism plays an important role in tuning of cGMP concentration in photoreceptors.
...
PMID:A novel role of RGS9: inhibition of retinal guanylyl cyclase. 1195 87


<< Previous 1 2 3 4 5 6 7 8 9 10

---