Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the repeated injection of sea urchin sperm guanylate cyclase into rabbits, antibodies to the enzyme were formed. These antibodies inhibited the particulate or the Triton-dispersed forms of the sperm enzyme by greater than 97%. The sperm adenylate cyclase, cyclic GMP phosphodiesterase, adenosine triphosphatase, guanosine triphosphatase, and 5'-nucleotidase enzymes were not affected by the antiserum. The antiserum inhibited the Triton-dispersed guanylate cyclase from rat heart, liver, lung, spleen, and kidney but did not inhibit the soluble form of the enzyme from any of these tissues. The inhibition of the Triton-dispersed enzyme in these tissues was partial, however, ranging from 30% (liver) to 70% (heart). These results provide evidence that adenylate cyclase is antigenically different from guanylate cyclase, and that the soluble form of guanylate cyclase is antigenically different from a particulate form of the enzyme in various rat tissues.
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PMID:Sea urchin sperm guanylate cyclase antibody. Cross-reactivity various rat tissue guanylate cyclases. 2 31

The present investigation describes kinetic characteristics of membrane-bound and Triton X-100-solubilized atrial natriuretic factor (ANF)-sensitive guanylate cyclase from bovine adrenal cortex. The kinetic analysis of both enzyme forms suggests that in the presence of manganese, ANF induces or stabilizes at least two apparent GTP*Mn2(+)- and in addition two Mn2(+)-binding sites. Addition of the natriuretic drug amiloride favors this state. ATP increases the vmax in the presence of ANF for GTP*Mg2+, but not for GTP*Mn2+ as a substrate. With GTP*Mg2+, amiloride has no effect on basal or ANF-stimulated activity, but slightly reduces the effect of ATP. Under all conditions tested, the enzyme follows regular Michaelis-Menten kinetics in the presence of Mg2+ and exhibits positive cooperativity with Mn2+. Positive cooperativity is also retained after Triton extraction. The results indicate that Triton extraction has no major influence on the kinetic properties of particulate guanylate cyclase when the extraction procedure is done carefully. The data also support the suggestion that multiple interactions of subunits might occur upon activation of the enzyme by ANF in the presence of Mn2+.
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PMID:Kinetic characterization of atrial natriuretic factor-sensitive particulate guanylate cyclase. 198 Jun 49

Urodilatin (ANF-(95-126] and beta-ANF, the antiparallel dimer of ANF-(99-126), are naturally occurring members of the ANF family. We studied their receptor binding properties in human platelets and Triton-solubilized membranes from bovine adrenal cortex and their ability to activate particulate guanylate cyclase in bovine adrenal cortex. In human platelets containing R2-receptors not coupled to particulate guanylate cyclase urodilatin binds with similar affinity as ANF-(99-126) (KD: 55 pM), whereas beta-ANF has an affinity lower than the truncated ANF-(103-123) (KD: 295 pM and 154 pM). Scatchard analysis indicates one binding site for urodilatin as well as for beta-ANF. In adrenal cortex containing predominantly R1-receptors coupled to particulate guanylate cyclase, urodilatin binds with a higher affinity (KD: 30 pM) than ANF-(99-126) (KD: 52 pM) and stimulates to a similar extent to ANF-(99-126) (about two fold at 1 muM), whereas beta-ANF has a smaller affinity (KD: 120 pM) and stimulates particulate guanylate cyclase to a lower extent than ANF-(99-126). The data from platelets and adrenal cortex show that beta-ANF has low binding affinities but stimulates particulate guanylate cyclase, whereas urodilatin appears to be a physiological R1-agonist.
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PMID:Urodilatin and beta-ANF: binding properties and activation of particulate guanylate cyclase. 257 May 74

Dictyostelium discoideum cells have been generated that lack myosin heavy chain (MHC) due to antisense RNA inactivation of the endogenous mRNA or to insertional mutagenesis of the myosin gene. These cells retain chemotactic movement in gradients of the chemoattractant cAMP. Furthermore, cAMP does induce many biochemical and physiological responses in aggregative cells, including binding of cAMP to surface receptors, modification, and down-regulation of the receptor; activation of adenylate and guanylate cyclase, secretion of cAMP; and the association of actin to the Triton-insoluble cytoskeleton. Cells lacking MHC were found to have a requirement for bivalent cations in the medium for optimal chemotaxis and cell aggregation.
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PMID:Signal transduction, chemotaxis, and cell aggregation in Dictyostelium discoideum cells without myosin heavy chain. 283 47

Guanylate cyclase was purified 12,700-fold from bovine brain supernatant, and the purified enzyme exhibited essentially a single protein band on polyacrylamide gel electrophoresis. Repeated injection of the purified enzyme into rabbits produced an antibody to guanylate cyclase. The immunoglobulin G fraction from the immunized rabbit gave only one precipitin line against the purified guanylate cyclase and the crude supernatant of bovine brain on double immunodiffusion and immunoelectrophoreis. The antibody completely inhibited the soluble guanylate cyclase activity from bovine brain, various tissues of rat and mouse and neuroblastoma N1E 115 cells, whereas the Triton-dispersed particulate guanylate cyclase from these tissues was not inhibited by the antibody.
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PMID:Production and properties of antibody to soluble guanylate cyclase purified from bovine brain. 610 90

Soluble guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) from rat lung demonstrated concentration-dependent stimulation, that is, an increase in specific activity with increasing enzyme (protein) concentration. This phenomenon persisted through several steps of enzyme purification and was apparently due to the presence of a macromolecular activator, similar in size to the enzyme. Treatment of partially purified enzyme with N-ethylmaleimide destroyed catalytic activity, but did not effect the ability of the preparation to stimulate activity. Kinetic analysis demonstrated that the stimulation was due to an increased V value with no change in the apparent Km value for MnGTP. Stimulation occurred without a time lag, the activator apparently interacting reversibly with the enzyme to increase catalytic capability. Some nonionic detergents of the Triton series inhibited enzyme activity by decreasing the V value, with no change in the Km value, and also decreased concentration-dependent stimulation. However, the two phenomena were not directly related. While the physiological significance of the activator is unclear, its presence affects estimations of recovery during enzyme purification, V determinations, and determinations of the effect of hormone or drug treatment on the activity of tissue extracts.
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PMID:Kinetic effects of the concentration-dependent stimulation of soluble guanylate cyclase from rat lung. 611 40

Endothelial-derived nitric oxide (NO) is an important intercellular messenger. Although endothelial cells contain both nitric oxide synthase and soluble guanylate cyclase, the nature of receptor proteins for cGMP is uncertain. Based on previous work in vascular smooth muscle cells which indicates that the cGMP-dependent protein kinase (cGK) is partially associated with the cytoskeleton, we determined that cGK was present in non-cytosolic fractions of endothelial cells. The data reveal that cGK is found only in Triton-soluble extracts of particulate fractions from bovine aortic endothelial cells and provide the first evidence for the existence of cGK in this cell type based on immunoreactivity, immunofluorescence microscopy and phosphotransferase activity. The limited distribution of endothelial cell cGK may explain why this kinase has not been heretofore identified in endothelial cells.
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PMID:Identification and possible localization of cGMP-dependent protein kinase in bovine aortic endothelial cells. 800 83