Opposing adenine nucleotide-dependent pathways regulate guanylyl cyclase C in rat intestine.

Parkinson, Scott J.; Carrithers, Stephen L.; Waldman, Scott A.

doi:10.1016/s0021-9258(17)31700-3

Cited by 40 publications

(28 citation statements)

References 38 publications

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“…The precise mechanisms mediating allosteric inhibition of GCC by adenine nucleotides remain unclear. Earlier studies demonstrated that this inhibition was associated with a shift in the kinetics of GCC from positive to negative cooperativity (Parkinson et al, 1994). These observations are consistent with the hypothesis that adenine nucleotide inhibition of GCC is mediated by a guanine nucleotide-dependent mechanism.…”

supporting

confidence: 88%

“…Guanylyl Cyclase Assay. Guanylyl cyclase activity was assayed as described previously (Parkinson et al, 1994). Membranes were incubated at 37 °C in a final volume of 100-400 µL in the presence of 50 mM Tris-HCl (pH 7.6) containing 500 µM IBMX, 7.5 mM creatine phosphate/20 µM creatine phosphokinase, GTP, manganese or magnesium chloride (3 mM in excess of nucleotide), and adenine nucleotide, where indicated.…”

Section: Methodsmentioning

confidence: 99%

“…Following acetylation, samples were diluted with 50 mM sodium acetate (pH 4.0) containing 20 mM CaCl 2 (Patrinellis et al, 1994). Cyclic GMP was quantified by radioimmunoassay, as described previously (Parkinson et al, 1994). Radioimmunoassays were performed in triplicate and enzyme reactions in duplicate, and results are representative of at least 3 experiments.…”

Section: Methodsmentioning

confidence: 99%

“…However, the role of ATP in coupling receptor occupancy and catalytic activation has been confounded by the observation that adenine nucleotides inhibit GCC when manganese, rather than magnesium, serves as the substrate cofactor (Gazzano et al, 1991a,b;Marala et al, 1991). Recently, adenine nucleotide-dependent inhibition of basal and ligand-stimulated GCC was demonstrated to be, in part, allosteric, independent of the substrate cation cofactor, and pharmacologically distinct from the activation of GCC by ATP (Parkinson et al, 1994).…”

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confidence: 99%

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An Intracellular Adenine Nucleotide Binding Site Inhibits Guanylyl Cyclase C by a Guanine Nucleotide-Dependent Mechanism

Parkinson

1996

Biochemistry

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Guanylyl cyclase C (GCC), the receptor for the Escherichia coli heat-stable enterotoxin (ST), is inhibited by 2-substituted adenine nucleotides in an allosteric fashion. In confluent cultures of Caco-2 intestinal epithelial cells, extracellular 2-methylthioadenosine triphosphate (2MeSATP) had no effect on basal or ST-stimulated cyclic GMP (cGMP) accumulation. However, this nucleotide inhibited cGMP accumulation in digitonin-permeabilized Caco-2 human colon carcinoma cells, demonstrating that allosteric inhibition of GCC by adenine nucleotides is mediated by an intracellular adenine nucleotide binding site rather than purinergic receptors. The role of guanine nucleotides in the regulation of GCC by adenine nucleotides was examined. Increasing GTP concentrations from 5 to 100 microM increased the potency of 2MeSATP inhibition of GCC 20-fold, with a shift in the Ki from 447 to 22 microM, respectively. Also, the hydrolysis-resistant analogue, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), supported 2MeSATP inhibition of GCC with a potency which was 10-fold greater than GTP. In addition, GTP alone, in the absence of adenine nucleotides and at concentrations greater than 1 mM, inhibited GCC through a mechanism convergent with 2MeSATP. Guanine nucleotides supported adenine nucleotide inhibition of GCC at low concentrations and directly inhibited this enzyme at high concentrations when these studies were conducted with receptors expressed in Caco-2 cells, native rat intestine, or cloned rat GCC heterologously expressed in 293 monkey kidney cells. These observations demonstrate that adenine nucleotide inhibition of GCC is mediated through an intracellular mechanism which is guanine nucleotide-dependent.

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supporting

confidence: 88%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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An Intracellular Adenine Nucleotide Binding Site Inhibits Guanylyl Cyclase C by a Guanine Nucleotide-Dependent Mechanism

Parkinson

1996

Biochemistry

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“…Guanylyl cyclases belong to the Class III nucleotide cyclase family. Homodimeric receptor GCs could have two active sites, and the allostery seen in biochemical assays suggests that there are indeed two substratebinding sites per dimer of enzyme (Parkinson et al 1994). Recent crystal structures of the guanylyl cyclases Cya2 from cyanobacterium Synechocystis PCC6803 and CYG12 from the green algae Chlamydomonasreinhardtii reveal the presence of a head-to-tail homodimer with the two monomers in a wreath-like arrangement.…”

Section: Mode Of Activation and Regulationmentioning

confidence: 99%

Gaba

2018

Encyclopedia of Signaling Molecules

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G alpha o 1893G regulators of the Gao protein may provide a cellspecific mechanism for Gao-regulated signaling pathways. PTX catalyzes the ADP-ribosylation of the a subunits of the Go, Gi, and Gt proteins at the C-terminal cysteine residue (À4 position). This prevents the G protein from interacting with GPCRs on the cell membrane, thus interfering with intracellular signaling. 1896 G alpha o G alpha o 1897 G cyclase, guanylate cyclase, Rap1 GTPaseactivating protein (Rap1GAP), axin, and pins. Compartmentalization of these signaling molecules in membrane rafts may ensure specificity and fidelity in Gao signaling. Go is the most abundant G protein in the central nervous system, where it comprises about 1% of membrane proteins in the mammalian brain. Go regulates neuronal development, memory, visual reception, olfactory reception, and taste reception. It is also localized in heart tissue and implicated in heart contractility. Its expression is regulated during the development of the brain and heart. Somatic mutations in the GNAO1 gene induce human cancers by rendering Gao constitutively activated. Heterozygous mutations in the GNAO1 gene cause epileptic encephalopathy by destabilizing Gao. Gao-deficient mice have several neurological deficits, including tremors, seizures, hyperalgesia, motor control impairment, and olfactory impairment. Muscarinic regulation of heart rate and heart rate variability is also impaired in Gao-deficient mice. Drosophila melanogaster mutants with loss of function of Gao show impaired morphogenesis of the heart and epithelial polarity of cardiac cells and abnormal sleep. Gao-deficient C. elegans has phenotypes including neuronal migration defects, hyperactive locomotion, and egg laying.

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Acid‐Base Properties of Adenosine 5′‐O‐Thiomonophosphate in Aqueous Solution

Song¹,

Sigel²,

Sigel³

1997

Chemistry A European J

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Abstract:The acidity constants of H,-(AMPS)' were determined by potentiometric pH titrations in aqueous solution at 25 "C and Z = 0.1 M (NaNO,). Titrations with a combined single-junction glass electrode were hampered in the presence of AMPS by a "poisoning" effect; the problem could be avoided by use of two separated electrodes. The values of 3.72f0.03 and pK:,A,,s, = 4.83F0.02 are relatively close to each other; the buffer regions of the two equilibria overiap, and therefore a micro acidity constant scheme was developed and the conthe acidity constants pK,&AMps, --

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Opposing adenine nucleotide-dependent pathways regulate guanylyl cyclase C in rat intestine.

Cited by 40 publications

References 38 publications

An Intracellular Adenine Nucleotide Binding Site Inhibits Guanylyl Cyclase C by a Guanine Nucleotide-Dependent Mechanism

An Intracellular Adenine Nucleotide Binding Site Inhibits Guanylyl Cyclase C by a Guanine Nucleotide-Dependent Mechanism

Gaba

Acid‐Base Properties of Adenosine 5′‐O‐Thiomonophosphate in Aqueous Solution

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