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

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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)

Luminal brush border and contraluminal basal-lateral segments of the plasma membrane from the same kidney cortex were prepared. The brush border membrane preparation was enriched in trehalase and gamma-glutamyltranspeptidase, whereas the basal-lateral membrane preparation was enriched in (Na+ + K+1)-ATPase. However, the specific activity of (Na+ + K+)-ATPase in brush border membranes also increased relative to that in the crude plasma membrane fraction, suggesting that (Na+ + K+)-ATPase may be an intrinsic constituent of the renal brush border membrane in addition to being prevalent in the basal-lateral membrane. Adenylate cyclase had the same distribution pattern as (Na+ + K+)-ATPase, i.e. higher specific activity in basal-lateral membranes and present in brush border membranes. Adenylate cyclase in both membrane preparations was stimulated by parathyroid hormone, calcitonin, epinephrine, prostaglandins and 5'-guanylylimidodiphosphate. When the agonists were used in combination enhancements were additive. In contrast to the distribution of adenylate cyclase, guanylate cyclase was found in the cytosol and in basal-lateral membranes with a maximal specific activity (NaN3 plus Triton X-100) 10-fold that in brush border membranes. ATP enhanced guanylate cyclase activity only in basal-lateral membranes. It is proposed that guanylate cyclase, in addition to (Na+ + K+)-ATPase, be used as an enzyme "marker" for the renal basal-lateral membrane.
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PMID:Preparation of renal cortex basal-lateral and bursh border membranes. Localization of adenylate cyclase and guanylate cyclase activities. 1 97

The activity of the enzyme, guanyl cyclase, associated with the rat intestinal brush border membrane, has an endogenous circadian rhythm which is observed in the absence of oral intermittent feeding and of a dark period. This rhythm is cued by the feeding schedule but is essentially unaffected by a light-dark cycle.
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PMID:Evidence for circadian rhythmicity in guanyl cyclase of the rat intestinal epithelial cell. 3 71

We report here the molecular characterization of a recombinant cell line (293-STaR) expressing the heat-stable enterotoxin receptor (STaR) from human intestine. We have compared the 293-STaR cell line with the human colonic cell line T84 that endogenously expresses STa binding sites. Scatchard analysis of displacement binding studies revealed a single STa binding site with an affinity (Ki) of 97 pM in 293-STaR compared with 55 pM in T84 cells. Saturation isotherms of STa binding gave a Kd of 94 pM for the cloned receptor expressed in 293 cells and 166 pM for the receptor present in T84 cells. Kinetic measurements of STa binding to 293-STaR gave an association rate constant, K1, of 2.4 x 10(8) M-1 min-1 and a dissociation rate constant, K2, of 0.016 min-1. The half-time of dissociation was 43 min, and the Kd calculated from the ratio of the kinetic constants was 67 pM. The pH profile of STa binding showed that the number of STa binding sites is increased 3-fold at pH 4.0 compared with pH 7.0, with no effect on binding affinity. A polyclonal antibody directed against the extracellular domain of STaR immunoprecipitated two proteins of approximately 140 and 160 kDa from both 293-STaR and T84 cells. Cross-linking of 125I-STa to 293-STaR cells resulted in the labeling of proteins with a molecular mass of approximately 153, 133, 81, 68, 56, and 49 kDa, the two smallest being the more abundant. Similar results have been reported for the STaR present on rat brush border membranes. These data suggest that the STaR-guanylyl cyclase identified by molecular cloning is the only receptor for STa present in T84 cells.
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PMID:Characterization of the recombinant human receptor for Escherichia coli heat-stable enterotoxin. 131 5

Undernutrition in human infants is associated with more prolonged episodes of diarrheal disease. Therefore, we tested the hypothesis that malnutrition prolongs the duration of Escherichia coli heat-stable enterotoxin-induced rat jejunal secretion. At weaning, rats were separated into two groups: malnourished rats were fed 50% of the previous day's intake of the fully fed control group. After approximately 2 wk of pair feeding, when malnourished rats weighed less than or equal to 60% of the full fed control group, we measured the secretory response to heat-stable enterotoxin in ligated jejunal loops. Toxin-induced secretion was equal in both groups until 30 min incubation time, after which net secretion continued to increase in the malnourished group but decreased in the fully fed group. Jejunal brush border membranes prepared from malnourished and fully fed rats demonstrated similar heat-stable enterotoxin receptor density, avidity of binding and guanyl cyclase activation. In both groups, radiolabeled toxin injected into in situ jejunal loops was converted into an altered radioligand unable to bind to brush border membranes. However, in malnourished rats, there was both increased appearance of two additional radioligands that still retained their ability to bind to brush border membranes and persistence of biologically active unlabeled toxin as measured in the suckling mouse bioassay. Our studies demonstrate that reduced or delayed inactivation of heat-stable enterotoxin, with continued presence of active toxin species, may contribute to prolonged secretion in the jejunum of malnourished rats.
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PMID:The jejunal secretory response to Escherichia coli heat-stable enterotoxin is prolonged in malnourished rats. 134 76

Certain nucleotides were found to regulate the binding of the Escherichia coli heat-stable enterotoxin (STa) to its receptor in pig intestinal brush border membranes. ATP and adenine nucleotide analogues inhibited 125I-STa binding, while guanine nucleotide analogues stimulated binding, with maximal effects at 0.5-1.0 mM. The strongest inhibitors were adenosine 5'-[beta gamma-imido]triphosphate (App[NH]p) (36%) and adenosine 5'-[beta-thio]diphosphate (ADP[S]) (41%). Inhibition did not require Mg2+, and was blocked by p-chloromercuribenzenesulphonate (PCMBS). Stimulation of binding required Mg2+, was not prevented by PCMBS and was maximal with GDP[S] (41%). While App[NH]p and MgGDP[S] appeared to be acting at different sites, they also interfered with each other. These nucleotides exerted only inhibitory effects on STa-stimulated guanylate cyclase activity, in contrast with the stimulatory effects of adenine nucleotides on atrial natriuretic peptide (ANP)-stimulated guanylate cyclase. Inhibition by low concentrations of MgApp[NH]p and MgATP was weaker above 0.1 mM, while MgGDP[S] and magnesium guanosine 5'-[gamma-thio]triphosphate (MgGTP[S]) inhibited in a single phase. Inhibition by MgApp[NH]p, at all concentrations, was competitive with the substrate (MgGTP), as was that by MgGDP[S] and MgGTP[S]. Whereas membrane guanylate cyclases usually show positively co-operative kinetics with respect to the substrate, STa-stimulated activity exhibited Michaelis-Menten kinetics with respect to MgGTP. This changed to positive co-operativity when Lubrol PX was the activator, or when the substrate was MnGTP. These results suggest the presence of both a regulatory and a catalytic nucleotide-binding site, which do not interact co-operatively with STa activation.
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PMID:Nucleotide regulation of heat-stable enterotoxin receptor binding and of guanylate cyclase activation. 135 Apr 35

Conflicting data have been published in favor of or against a secretory effect of atrial natriuretic peptide (ANP) in the intestine. The reported effects resemble that of Escherichia coli heat-stable enterotoxin (ST). In this work the effects of ANP were studied in well established experimental systems and compared with that of ST. Both peptides induced a prompt secretion of water, Na, and Cl with no effects on K net transport in the in vivo rat perfused jejunum. The addition of ST, but not of ANP, evoked an increase of short circuit current in rat intestinal mucosa mounted in Ussing chambers. ST induced a significant increase in guanylate cyclase activity in intestinal homogenates, whereas ANP showed no effect. No binding sites for ANP were detected in basolateral or brush border membranes, nor in isolated enterocytes by a suction filtration technique. In conclusion, ANP acts as a short-lived intestinal secretagogue in the rat. Its mechanism of action is different from that of E. coli ST and appears to be indirect, since is not mediated by specific intestinal receptors and is not evident in vitro.
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PMID:Comparative effects of atrial natriuretic peptide and E. coli heat-stable toxin on rat intestinal transport. 135 25

Development of age-dependent resistance to enterotoxigenic Escherichia coli was studied, using isolated enterocytes and brush border membranes (BBM) from 7-day-old and 7-week-old pigs. Binding of 125I-labeled heat-stable (125I-STa) enterotoxin to enterocytes and BBM was specific, temperature- and time-dependent, saturable, and partially reversible. Scatchard analysis revealed a single class of receptors. Mean +/- SD avidity of binding (apparent affinity constant, Ka) of 125I-STa to enterocytes from 7-day-old and 7-week-old pigs was 2.14 +/- 0.29 x 10(8) and 2.72 +/- 0.25 x 10(8) L/mol, respectively. Numbers of STa receptors were calculated to be 64,903 +/- 2,900/enterocyte for 7-day-old pigs and 53,029 +/- 3,117/enterocyte for 7-week-old pigs. Numbers of STa receptors expressed per milligram of BBM protein from 7-day-old pigs were 2.66 x 10(11), compared with 2.29 x 10(11) for BBM from 7-week-old pigs. By 5 minutes after addition of STa to reaction mixtures, intracellular cyclic guanosine monophosphate concentration increased 13.9-fold in enterocytes from 7-day-old pigs and 8.7-fold in enterocytes from 7-week-old pigs. The particulate guanylate cyclase activity associated with BBM from 7-week-old pigs was slightly more sensitive to low amounts of STa, compared with BBM from 7-day-old pigs; however, differences were not observed at intermediate and high amounts. These data indicate that lack of a secretory response to STa by older pigs is not attributable either to decreased numbers of STa receptors or to decreased signal response between the STa receptor and membrane-bound guanylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of age on activation of porcine intestinal guanylate cyclase and binding of Escherichia coli heat-stable enterotoxin (STa) to porcine intestinal cells and brush border membranes. 136 45

The Na-H antiporter of renal-brush border membranes is inhibited by cyclic AMP and stimulated by protein kinase C. The proximal tubule contains guanylate cyclase and is capable of cyclic GMP production. The effect of cGMP on renal Na-H antiporter activity was analyzed in phosphorylated brush border membranes by 22Na uptake in the presence or absence of 1 mM amiloride. 8-Bromo cyclic GMP (1 microM) increased the amiloride-sensitive 22Na uptake in control from 1.26 +/- 0.13 to 1.54 +/- 0.12 nmol/mg/protein/10 sec, P less than 0.01, without altering the amiloride-insensitive component. In the absence of exogenous ATP, cGMP also stimulated the amiloride-sensitive 22Na uptake, which can be explained by the presence of endogenous ATP in concentrations of up to 50 microM in the membranes. In ATP-depleted membrane vesicles, however, cGMP inhibited the amiloride-sensitive 22Na uptake. These data indicate that cGMP acts on the Na-H antiporter by at least two different mechanisms, one of which is ATP dependent. It is likely that cGMP-dependent protein kinase mediates the stimulatory effects seen in the presence of ATP, and the inhibition seen in ATP-depleted membranes results from cGMP direct action on the Na-H antiporter.
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PMID:Dual effect of cyclic GMP on renal brush border Na-H antiporter. 165 8

Pigs demonstrate an increased sensitivity and susceptibility to Escherichia coli heat-stable enterotoxin (STa) in the 1st wk of life and immediately after weaning. To determine the possible mechanisms for this increased susceptibility, we compared STa binding, guanylate cyclase activation, and photoaffinity cross-linking to porcine jejunal brush border membranes prepared from immature (less than or equal to 1 wk of age) versus adult pigs as well as 3-wk-old weaned versus unweaned pigs. The STa binding capacity of immature pigs was nearly twice that of adult pigs (11.73 +/- 1.52 versus 6.00 +/- 0.96 x 10(-11) mol/L, p less than 0.001), and the STa binding capacity of weaned pigs was nearly three times greater than that of unweaned pigs (17.48 +/- 2.10 versus 4.86 +/- 1.02 x 10(-11) mol/L, p less than 0.001). Scatchard analysis suggested a single class of STa receptor, with an association of binding constant of approximately 10(9) L/mol at all ages. Maximum guanylate cyclase response (expressed as pmol cyclic GMP generated/mg brush border membrane protein/min) was greater in immature versus adult pigs (1312 +/- 831 versus 320 +/- 92, p less than 0.02). Weaned pigs had a greater maximum guanylate cyclase activation than unweaned pigs (1126 +/- 692 versus 624 +/- 298); however, this difference was not statistically significant. Autoradiograms demonstrated specific cross-linking of 125I-STa to a number of distinct radiolabeled bands (62, 66, 84, 92, 160, and 165 kD). There was a difference in the size and trypsin sensitivity of these radiolabeled bands as a function of age and weaning. Treatment with trypsin decreased the intensity of the 160 to 165-kD bands while increasing the intensity of the 62- to 66- and 84- to 92-kD bands. These differences in STa binding, guanylate cyclase activation, and STa receptor size may increase the susceptibility of pigs during the 1st wk of life and at weaning to STa-mediated diarrheal disease.
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PMID:Mechanisms of increased susceptibility of immature and weaned pigs to Escherichia coli heat-stable enterotoxin. 168 Feb 29

Heat-stable enterotoxin (STa) produced by Escherichia coli induces intestinal secretion in mammals by binding to the brush border membrane of the small intestine and activating guanylyl cyclase. We report here the cloning and expression of a cDNA encoding the human receptor for STa. The receptor contains both an extracellular ligand binding site and a cytoplasmic guanylyl cyclase catalytic domain, making it a member of the same receptor family as the natriuretic peptide receptors. Stable mammalian cell lines over-expressing the STa receptor specifically bind 125I-STa (Kd approximately 1.0 nM) and respond to STa by dramatically increasing (approximately 50-fold) cellular cGMP levels. Sequence comparisons between the human and the rat STa receptors show less conservation in the extracellular domain than similar comparisons of natriuretic peptide receptors. This divergence may indicate important species differences in ligand-receptor interaction.
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PMID:Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin. 168 Aug 54


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