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

Sodium azide, hydroxylamine, and phenylhydrazine at concentrations of 1 mM increased the activity of soluble guanylate cyclase from rat liver 2- to 20-fold. The increased accumulation of guanosine 3':5'-monophosphate in reaction mixtures with sodium azide was not due to altered levels of substrate, GTP, or altered hydrolysis of guanosine 3':5'-monophosphate by cyclic nucleotide phosphodiesterase. The activation of guanylate cyclase was dependent upon NaN3 concentration and temperature; preincubation prevented the time lag of activation observed during incubation. The concentration of NaN3 that resulted in half-maximal activation was 0.04 mM. Sodium azide increased the apparent Km for GTP from 35 to 113 muM. With NaN3 activation the enzyme was less dependent upon the concentration of free Mn2+. Activation of enzyme by NaN3 was irreversible with dilution or dialysis of reaction mixtures. The slopes of Arrhenius plots were altered with sodium azide-activated enzyme, while gel filtration of the enzyme on Sepharose 4B was unaltered by NaN3 treatment. Triton X-100 increased the activity of the enzyme, and in the presence of Triton X-100 the activation by NaN3 was not observed. Trypsin treatment decreased both basal guanylate cyclase activity and the responsiveness to NaN3. Phospholipase A, phospholipase C, and neuraminidase increased basal activity but had little effect on the responsiveness to NaN3. Both soluble and particulate guanylate cyclase from liver and kidney were stimulated with NaN3. The particulate enzyme from cerebral cortex and cerebellum was also activated with NaN3, whereas the soluble enzyme from these tissues was not. Little or no effect of NaN3 was observed with preparations from lung, heart, and several other tissues. The lack of an effect with NaN3 on soluble GUANYLATE Cyclase from heart was probably due to the presence of an inhibitor of NaN3 activation in heart preparations. The effect of NaN3 was decreased or absent when soluble guanylate cyclase from liver was purified or stored at -20degrees. The activation of guanylate cyclase by NaN3 is complex and may be the result of the nucleophilic agent acting on the enzyme directly or what may be more likely on some other factor in liver preparations.
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PMID:Activation of guanylate cyclase from rat liver and other tissues by sodium azide. 24 Aug 48

We have studied the structure and function of the membrane atrial natriuretic factor R1 (ANF-R1) receptor using limited proteolysis and exoglycosidase treatment. Limited digestion with trypsin of the receptor from bovine adrenal zona glomerulosa membranes resulted in the conversion of the native 130-kDa receptor into a single membrane-associated ANF-binding proteolytic fragment of 70 kDa. The 70-kDa fragment bound ANF with enhanced binding affinity but retained intact ANF-R1 pharmacological specificity and was still sensitive to modulation by amiloride. Trypsin treatment of the membranes produced a dual effect on ANF binding. Low concentrations of trypsin (less than or equal to 25 micrograms/mg of protein) increased ANF binding while higher concentrations dose dependently reduced the binding of the hormone. The increase of ANF-binding activity was associated with the formation of the 70-kDa fragment while the loss of ANF binding paralleled the degradation of the 70-kDa fragment. Low concentrations of trypsin drastically decreased the ANF-sensitive guanylate cyclase activity of the membrane fraction. This loss of catalytic activity strongly correlated with the formation of the 70-kDa tryptic fragment. We also evaluated the effect of ANF binding on the susceptibility of the receptor to proteolytic cleavage. The occupied receptor exhibited a greater sensitivity to trypsin digestion than the unoccupied protein, consistent with the hypothesis that hormone binding induces an important conformational change in the receptor structure. On the other hand, the 70-kDa fragment was much more resistant to proteolysis when occupied by ANF, suggesting that the ANF-binding domain forms a very compact structure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Topographical characterization of the domain structure of the bovine adrenal atrial natriuretic factor R1 receptor. 255 56

The effects on guanylate cyclase and cyclic GMP accumulation of a synthetic peptide containing the amino acid sequence and biological activity of atrial natriuretic factor (ANF) were studied. ANF activated particulate guanylate cyclase in a concentration- and time- dependent fashion in crude membranes obtained from homogenates of rat kidney. Activation of particulate guanylate cyclase by ANF was also observed in particulate fractions from homogenates of rat aorta, testes, intestine, lung, and liver, but not from heart or brain. Soluble guanylate cyclase obtained from these tissues was not activated by ANF. Trypsin treatment of ANF prevented the activation of guanylate cyclase, while heat treatment had no effect. Accumulation of cyclic GMP in kidney minces and aorta was stimulated by ANF activation of guanylate cyclase. These data suggest a role for particulate guanylate cyclase in the molecular mechanisms underlying the physiological effects of ANF such as vascular relaxation, natriuresis, and diuresis.
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PMID:Atrial natriuretic factor selectively activates particulate guanylate cyclase and elevates cyclic GMP in rat tissues. 615 43