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)

Atrial natriuretic factor (ANF) cleaved between Cys105 and Phe106 is the primary metabolite of ANF and circulates in human plasma. Because the role of this metabolite in vivo and its possible interaction with intact ANF are unclear, we studied the biologic effects of a 2-h infusion of rat cleaved ANF101-105/106-126 (15 pmol/kg/min) or vehicle alone in six normal sheep. Infusions of cleaved ANF increased venous plasma levels of cleaved ANF from less than 5 to 260 pmol/L and induced a progressive and significant increase in plasma cyclic GMP (p = 0.025) without significantly affecting plasma ANF levels. These changes were associated with a small (nonsignificant) decrease in arterial pressure and a significant increase in heart rate (HR) and sympathetic nervous activity and were followed by activation of the renin-angiotensin-aldosterone (RAA) axis after infusions were terminated. Unlike ANF itself, cleaved ANF was not natriuretic and did not reduce plasma volume or right atrial pressure. Calculated metabolic clearance rate (MCR) (1.47 +/- 0.4 L/min) and disappearance rate of cleaved ANF from plasma (4.8 +/- 0.37 min) were similar to values reported previously for intact ANF in sheep. These studies show that cleaved ANF stimulates guanylate cyclase and alters hemodynamics and the RAA system in vivo.
...
PMID:Biological actions of cleaved atrial natriuretic factor (ANF101-105/106-126) in conscious sheep. 171 1

Microlocalization of mRNA coding for the guanylyl cyclase-coupled atrial natriuretic factor (ANF) receptor was carried out in the rat kidney. We used a combination of reverse transcription and polymerase chain reaction (RT-PCR) in individual microdissected renal tubule segments, glomeruli, and vasa recta bundles. Relative quantitation of the resulting amplified cDNA utilized densitometry of autoradiograms from Southern blots probed with a specific 32P-labeled probe. Among renal tubule segments, the largest signal was found in the terminal inner medullary collecting duct (IMCD). Slightly smaller signals were found in the initial IMCD and in loop of Henle segments from the inner medulla. Readily detectable signals were also seen in the following segments (in descending order): cortical collecting duct, proximal convoluted tubule, medullary thick ascending limb, cortical thick ascending limb, distal convoluted tubule, and outer medullary collecting duct. Large signals were also detected in glomeruli and in vasa recta bundles from the inner stripe of the outer medulla. Based on these results, we conclude that 1) renal microlocalization of specific mRNAs coding for hormone receptors is feasible through application of the RT-PCR procedure in microdissected renal tubules and vascular elements, and 2) the gene for the guanylyl cyclase-coupled ANF receptor is broadly expressed along the nephron, raising the possibility that multiple sites of ANF action are present.
...
PMID:RT-PCR microlocalization of mRNA for guanylyl cyclase-coupled ANF receptor in rat kidney. 172 96

Atrial natriuretic factor (ANF, 10(-7) M) and sodium nitroprusside (SNP, 10(-5)-10(-3) M) stimulated cGMP production in human peritoneal macrophages (HPM). This suggests the existence of two separate forms of guanylate cyclase in HPM, e.g. the receptor-related form by ANF and the soluble form by SNP. In parallel with the rise in cGMP levels, both agents provoked a decrease in cAMP levels. Increasing the concentration of the phosphodiesterase inhibitor IBMX (0.2 mM to 1.0 mM) in the incubation media resulted in a significantly greater rise in cGMP levels which was accompanied by a profound decrease in cAMP levels. ANF did not exert any direct or GTP-related effect on cAMP production, which is in contrast to its action in other tissues. These results suggest that cAMP levels can be modulated through a cGMP signal, most likely at the production level. Results also give substantial evidence for the presence of a ANF receptor site on human peritoneal macrophages.
...
PMID:Cyclic nucleotides in human macrophages: effects of atrial natriuretic factor and nitroprusside on cGMP and cAMP production. 172 23

To study the effect of atrial natriuretic factor (ANF) on airway ciliary motility, we measured ciliary beat frequency by a photoelectric method in response to ANF in cultured tracheal epithelial cells from rabbits. Addition of ANF but not [Tyr8]ANF-(5-27) decreased ciliary beat frequency in a dose-dependent fashion; the maximal decrease from the baseline value was 24.1 +/- 1.5% (+/- SE, P less than 0.001), and a half-maximal inhibitory concentration (IC50) was 3 x 10(-12) M. Inhibition of neutral endopeptidase activity by phosphoramidon (10(-6) M) or thiorphan (10(-6) M) potentiated the effect of ANF so that the dose-response curve for ANF was shifted to lower concentrations by approximately 0.5 log units (P less than 0.05, in each case). The inhibition of ciliary motility induced by ANF was not affected by the blockade of arachidonic acid metabolism with indomethacin, piroxicam, or nordihydroguaiaretic acid, but it was blocked by methylene blue, a soluble guanylate cyclase inhibitor, and was potentiated by M & B 22948, a guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase inhibitor. The intracellular cGMP levels were increased by ANF, an effect that was further potentiated by phosphoramidon or thiorphan. These results suggest that ANF inhibits ciliary motility presumably through a guanylate cyclase-dependent regulatory pathway and that neutral endopeptidase may play a role in modulating the ANF effect on airway mucociliary transport function.
...
PMID:Atrial natriuretic factor inhibits ciliary motility in cultured rabbit tracheal epithelium. 182 49

The cardiovascular effects of endothelin-1 (ET-1) in trout were examined in unanesthetized fish, perfused tissues, and isolated vascular rings. In vivo, a bolus of 500 ng/kg body wt ET-1 transiently lowered arterial (postgill) blood pressure (BP) by nearly 30%; 1,500 ng/kg body wt produced a triphasic, pressor-depressor-pressor, response. Continuous infusion of 0.1, 1, 10, and 30 ng.kg-1.min-1 progressively lowered BP but did not affect heart rate (HR), urine flow, or electrolyte excretion. In the in situ perfused heart ET-1 (10(-11) to 10(-8) M) had no effect on HR or power output. ET-1 produced dose-dependent increases in vascular resistance in the perfused gill, renal-skeletal muscle, and splanchnic circulations, and increased tension, independent of endothelium, in vascular rings from celiacomesenteric (CA) and coronary arteries and anterior cardinal veins (CV). Ventral aortas were refractory to ET-1. In vitro, ET-1 effects were slow in onset and long lasting. External calcium was required for maximal ET-1 responses in gill and CA. ET-1 effects on CA but not CV were partially inhibited by calcium channel blockers, diltiazem, and D 600, and by the guanylate cyclase activators, atrial natriuretic factor, and sodium nitroprusside. [3H]water flux across the perfused gill was stimulated by ET-1 through what appeared to be a vascular-independent mechanism. These experiments show that the trout vasculature is exquisitely sensitive to ET-1, and they suggest that the physiological expression of this peptide has been highly conserved during the course of vertebrate evolution.
...
PMID:Cardiovascular effects of endothelin in trout. 182 12

Atrial natriuretic peptide (ANP) binding and ANP-induced increases in cyclic guanosine monophosphate (cGMP) levels have been observed in brain microvessels (Chabrier et al., 1987; Steardo and Nathanson, 1987), suggesting that this fluid-regulating hormone may play a role in the fluid homeostasis of the brain. This study was initiated to characterize the ANP receptors in primary cultures of brain microvessel endothelial cells (BMECs). The apparent equilibrium dissociation constant, Kd, for ANP increased from 0.25 nM to 2.5 nM, and the number of ANP binding sites as determined by Scatchard analysis increased from 7,100 to 170,000 sites/cell between 2 and 10 days of culture following monolayer formation. Time- and concentration-dependent studies on the stimulation of cGMP levels by ANP indicated that guanylate cyclase-linked ANP receptors were present in BMECs. The relative abilities of ANP, brain natriuretic peptide (BNP), and a truncated analog of ANP containing amino acids 5-27 (ANP 5-27) to modulate the accumulation of cGMP was found to be ANP greater than BNP much greater than ANP 5-27. Affinity cross-linking with disuccinimidyl suberate and radiolabeled ANP followed by gel electrophoresis under reducing conditions demonstrated a single band corresponding to the 60-70 kD receptor, indicating the presence of the nonguanylate cyclase-linked ANP receptor. Radiolabeled ANP binding was examined in the presence of various concentrations of either ANP, BNP, or ANP 5-27 and suggested that a large proportion of the ANP receptors present in blood-brain barrier endothelial cells bind all of these ligands similarly. These data indicate both guanylate cyclase linked and nonguanylate cyclase linked receptors are present on BMECs and that a higher proportion of the nonguanylate cyclase linked receptors is expressed. This in vitro culture system may provide a valuable tool for the examination of ANP receptor expression and function in blood-brain barrier endothelial cells.
...
PMID:Characterization of atrial natriuretic peptide receptors in brain microvessel endothelial cells. 184 36

Atrial natriuretic peptide (ANP) exhibits a wide spectrum of cardiovascular, endocrine, metabolic and renal actions. cGMP is the major mediator of ANP at the cellular level and only tissues possessing particulate guanylate cyclase appear to present ANP-induced actions. Three types of ANP receptors have recently been cloned. Two of them (A and B receptors) are homologous and contain guanylate cyclase catalytic domains. The C receptor could possibly regulate the metabolic fate of ANP. Data obtained by the radiation inactivation method suggest the presence of an inter- or intramolecular inhibitory component of nearly 90 kilodaltons that represses the catalytic activity of guanylate cyclase within its membrane environment. The mechanism of guanylate cyclase stimulation by ANP could involve this inhibitory component. Preliminary data suggest that the hyperresponsiveness of the particulate guanylate cyclase/cGMP system in hypertension occurs through modulation of the inhibitory component.
...
PMID:Cell biology of atrial natriuretic peptide. 184 28

Previous studies have demonstrated that the biological actions of atrial natriuretic factor (ANF) are mediated via increases in its intracellular second messenger guanosine 3',5'-cyclic monophosphate (cGMP). Because cGMP egresses rapidly from target cells after ANF binding to particulate guanylate cyclase-linked receptors, extracellular cGMP may be a useful biological marker for the action of ANF in vivo under pathophysiological conditions. The present studies tested the hypothesis that the avid sodium retention and renal ANF resistance characteristic of chronic congestive heart failure (CHF) are associated with attenuated renal cGMP responses to ANF. We assessed the natriuretic and cGMP responses to endogenous and exogenous ANF during the evolution of CHF produced by 6 days of rapid ventricular pacing in conscious dogs (n = 6). Simultaneous measurement of plasma and urinary cGMP concentrations allowed determination of the net renal generation of cGMP, an indicator of the renal contribution to total urinary cGMP excretion. In early CHF, increased sodium excretion and renal cGMP production were observed in association with increases in plasma ANF. Exogenous ANF administration (10 micrograms/kg iv) before CHF also produced parallel increases in sodium excretion and renal cGMP production. In more advanced CHF produced by 6 days of pacing, we observed avid sodium retention in association with reversal of earlier increases in renal cGMP production despite progressive increases in circulating ANF. Natriuretic and renal cGMP responses to exogenous ANF were similarly attenuated in chronic CHF. These studies suggest that 1) renal cGMP production is a useful biological marker for the renal natriuretic action of ANF; 2) endogenous ANF contributes to the maintenance of sodium excretion in early CHF via increases in renal cGMP production; and 3) the avid sodium retention and renal ANF resistance in advanced CHF are, in part, linked to attenuated renal cGMP responses to endogenous and exogenous ANF.
...
PMID:ANF-mediated renal cGMP generation in congestive heart failure. 184 64

In spite of its pivotal role in visual transduction, very little is known about guanylate cyclase of retinal photoreceptor cells. The enzyme has not yet been purified principally because of the difficulty in solubilizing it. We report here a simple method for solubilization of 67% of the cyclase activity from the retinal rod disk membranes (RDM). With Nonidet P-40 as detergent, the solubilization of cyclase is favored by a high concentration of KCl and exclusion of manganese. The solubilized and the residual insoluble enzymes are both highly unstable but could be partially stabilized by dithiothreitol. They were both insensitive to calcium, calmodulin, and atrial natriuretic factor. They also responded similarly to varying the manganese concentration in the assay. For the activity in both fractions, the Km for GTP was about 230 microM, Line-weaver-Burk plots showed that substrate binding was cooperative, and Hill plots suggested that there are two substrate binding sites. Cumulatively, these observations showed that while the entire activity could not be solubilized, the solubilized and the residual insoluble activities probably belonged to the same enzyme. Partial purification resolved the solubilized enzyme into two activities refered to as enzymes 1 and 2. Both had substrate saturation kinetics similar to the solubilized enzyme and were inhibited competitively by inorganic pyrophosphate, one of the products of the cyclase reaction. The Ki for PPi for enzyme 1 was 70-100 microM and 150-200 microM for enzyme 2. cGMP at concentrations up to 800 microM had no influence on the activity of either enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Guanylate cyclase from bovine rod outer segments: solubilization, partial purification, and regulation by inorganic pyrophosphate. 197 Nov 84

The present studies were initiated to determine if cells of intestinal origin possess the molecular components supporting a response to atrial natriuretic peptides. Specific binding in cultured rat ileal cells with 125I-labeled atrial natriuretic peptide was saturable and of high affinity. Scatchard analyses showed a single population of binding sites with a Kd of 2.1 nmol/L and a Bmax of 300 fmol/mg protein. Atrial natriuretic peptide activated particulate guanylate cyclase 5- to 10-fold in a concentration- and time-dependent fashion. The EC50 for activation of enzyme by atrial natriuretic peptide was 6 nmol/L. Accumulation of cyclic guanosine monophosphate stimulated by atrial natriuretic peptide was observed in the intracellular (25-fold) and extracellular (50-fold) compartments and was dependent on concentration and time. Half-maximum intracellular accumulation was observed with 10 nmol/L atrial natriuretic peptide. These data suggest a role for atrial natriuretic peptides in the gastrointestinal tract.
...
PMID:Rat intestinal cell atrial natriuretic peptide receptor coupled to guanylate cyclase. 197 6


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

---