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)

Atrial natriuretic factor (ANF) produced rapid increases in cyclic GMP (cGMP) in cultured aortic smooth muscle cells. Angiotensin II (ANG II) markedly decreased the accumulation of cGMP that was evoked by ANF. Arginine vasopressin and ATP, which evoke transient increases in free Ca2+ similarly to ANG II, also inhibited cGMP accumulation. The effect of the calcium mobilizing neurohormones was mimicked by the divalent cation ionophore, A23187. The cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, prevented ANG II from inhibiting ANF-evoked cGMP accumulation. ANG II also inhibited cGMP accumulation induced by nitroprusside, a compound that activates cytosolic guanylate cyclase. These findings support the hypothesis that ANG II decreases cGMP accumulation by stimulating cGMP hydrolysis, apparently via a Ca2+-activated cGMP phosphodiesterase.
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PMID:Angiotensin decreases cyclic GMP accumulation produced by atrial natriuretic factor. 244 Mar 11

Administration of atrial natriuretic factor (ANF) in animals results in increases in renal blood flow, natriuresis, and a decrease in arterial blood pressure, supporting a role for the atrial peptide system in cardiovascular regulation. However, little is known about the vascular effects of synthetic ANF (26 amino acid) on coronary artery smooth muscle. We studied the coronary vascular effects of synthetic ANF in feline artery preparations in vitro. In isolated coronary arteries perfused at constant flow, ANF (3-300 nM) concentration dependently decreased perfusion pressure ranging from 2.6 +/- 0.7 mm Hg (p less than 0.02) at 3 nM to 28.6 +/- 3.7 mm Hg (p less than 0.001) at 300 nM. Perfusion with the prostacyclin analog, iloprost (20-100 nM), failed to alter the coronary vasodilator response to ANF. ANF also relaxed feline coronary helical strips when contracted by U-46,619 (an endoperoxide analog), serotonin, and leukotriene D4. This relaxant effect was independent of the presence of endothelial cells and occurred in the presence of a guanylate cyclase inhibitor, methylene blue. The ANF had no direct effect on electrically driven isolated feline papillary muscles, signifying a lack of direct inotropic activity of ANF in cat cardiac muscle. These results suggest that ANF may produce coronary vasodilation that therefore could contribute to coronary regulation, without directly altering myocardial performance.
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PMID:Coronary vascular actions of synthetic atrial natriuretic factor in isolated vascular preparations. 244 81

Atrial natriuretic peptide (ANP) stimulates cGMP production in isolated rabbit ventricular myocytes incubated in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (1mM). Half maximal activation was found at 10(-8)M ANP. Cellular cGMP concentrations of around 0.6 pmol/10(6) cells were elevated 4-6 fold by ANP (10(-6)M), 3-4 fold by carbachol (1mM) and around 10 fold by sodium nitroprusside (1mM). ANP had no effect on basal or isoprenaline-stimulated cAMP concentrations or on basal or noradrenaline-stimulated turnover of phosphatidylinositol. From these results we conclude that ANP receptors, coupled to particulate guanylate cyclase, exist in cardiac ventricular muscle. This indicates that ANP may also have a physiological action on ventricular muscle contractility during volume expansion.
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PMID:Actions of atrial natriuretic peptide (ANP) on cyclic nucleotide concentrations and phosphatidylinositol turnover in ventricular myocytes. 244 14

The natriuretic agent amiloride induces a shift of the dose-response curve of particulate guanylate cyclase to atrial natriuretic factor (ANF) to the left. The ANF concentration for half-maximal activation of guanylate cyclase is shifted from 20 to 3 nM in the presence of 100 microM amiloride. This effect is observed with GTP*Mn2+, but not with GTP*Mg2+ as substrate. Amiloride derivatives, which inhibit a specific Na+-channel, also shift the dose-response curve to the left. These data suggest that some of the effects of amiloride may be mediated by an increased sensitivity of particulate guanylate cyclase to ANF.
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PMID:Amiloride increases the sensitivity of particulate guanylate cyclase to atrial natriuretic factor. 245 2

The effects of leukotriene D4 (LTD4) on guanosine 3',5'-cyclic monophosphate (cGMP) production induced by atrial natriuretic factor (ANF) or sodium nitroprusside (SNP) were investigated in isolated rat glomeruli. First, the isolated glomeruli were preincubated in Krebs-Ringer buffer containing 3-isobutyl-1-methylxanthine for 10 min, then incubated with varying concentrations of ANF, SNP, and LTD4 for 3 min. cGMP content was determined by radioimmunoassay. cGMP production (fmol.glomerulus-1.3 min-1) was not increased by LTD4. cGMP accumulation was increased by ANF (1 microM) and SNP (100 microM) remarkably from 0.19 +/- 0.09 to 3.24 +/- 0.21 (n = 7, mean +/- SE), and from 0.19 +/- 0.09 to 3.67 +/- 0.47 (n = 4), respectively. The increase in cGMP production by ANF was significantly and dose-dependently inhibited by LTD4 (P less than 0.05). Maximum suppression was observed at the concentration of 100 nM (from 3.06 +/- 0.33 to 1.43 +/- 0.09; P less than 0.05). However, LTD4 caused no significant change in the level of cGMP production induced by SNP. Second, particulate or soluble guanylate cyclase from glomeruli were similarly investigated. ANF selectively activated particulate guanylate cyclase and the response was selectively inhibited by LTD4 from 9.07 +/- 1.79 fmol.micrograms-1.3 min-1 (n = 6) to 4.70 +/- 0.70 (n = 6, P less than 0.05). These results suggest the site where LTD4 has effect on cGMP production induced by ANF was the particulate guanylate cyclase system, but not the soluble guanylate cyclase system.
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PMID:Leukotriene D4 inhibits atrial natriuretic factor-dependent cGMP production in rat glomerulus. 246 71

Effects of atrial natriuretic peptides (ANP) on the tension, content of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) and activity of particulate and soluble forms of guanylate cyclase were examined in bovine tracheal smooth muscle. Atrial natriuretic factor (ANF), atriopeptin II, and atriopeptin III were found to induce relaxation of tracheal smooth muscle precontracted with 5 x 10(-8) M carbachol (an approximate median effective concentration) in a concentration-dependent manner. However, atriopeptin I failed to induce significant relaxation of the muscle. Similar results were obtained when 3 x 10(-6) M histamine or 5 x 10(-7) M serotonin was used as the contracting agent. However, the relaxant effects of ANF, atriopeptin II, and atriopeptin III were much less when a higher concentration of carbachol or 30 mM K+ was used as the contractile agent. Maximally inhibitory concentration (IC50) values of ANF, atriopeptin II, and atriopeptin III for inhibition of muscle contraction induced by 5 x 10(-8) M carbachol ranged from 3.8 to 8.3 x 10(-9) M, indicating that these peptides have intermediate potency between isoproterenol (IC50, 2.0 x 10(-9) M) and sodium nitroprusside (IC50, 2.0 x 10(-8) M). Treatment of the muscle with 3 x 10(-7) M ANF slowed the rate of tension development of the muscle by 10(-7) M carbachol. Tissue levels of cAMP were not influenced by any of the atrial peptides at concentrations of 10(-9)-10(-6) M; however, cGMP levels were increased about five- to ninefold.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ANP relaxes bovine tracheal smooth muscle and increases cGMP. 246 7

The Purkinje fibers of the rabbit false tendons (chordae tendineae spuriae) are endocrine cells containing immunoreactive atrial natriuretic factor (ANF) and ANF messenger RNA (mRNA). These cells, as visualized by immunocryoultramicrotomy, contain immunoreactive ANF in their secretory granules and their Golgi complex and exhibit ANF mRNA, as visualized by in situ hybridization with an ANF complementary RNA probe. The content of immunoreactive ANF and ANF mRNA of the Purkinje fibers is midway between that of atrial and ventricular working cardiocytes. High-pressure liquid chromatography analysis of immunoreactive ANF using antibodies against the C-terminal and N-terminal moieties of the molecule indicates that part of immunoreactive ANF contained in Purkinje fibers is the propeptide [Asn1,Tyr126]ANF whereas part was nonspecifically cleaved into C-terminal and N-terminal ANF. The chordae tendineae spuriae exhibit binding sites for ANF (Kd:approximately 1.0 nM; Bmax:approximately 2.3 fmol/mg). ANF profoundly decreases basal and stimulated (epinephrine, dopamine, isoproterenol, and forskolin) adenylate cyclase activity and cyclic adenosine monophosphate (AMP) levels. ANF has little effect on norepinephrine-stimulated adenylate cyclase activity or on norepinephrine-stimulated cyclic AMP levels. ANF produces only a slight increase in guanylate cyclase activity and cyclic guanosine monophosphate levels at high (10(7)-10(6) M) concentrations. These results suggest an autocrine function for ANF in the modulation of the impulse in the peripheral conduction cells (Purkinje fibers) of the rabbit through changes in second messenger levels.
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PMID:Atrial natriuretic factor in Purkinje fibers of rabbit heart. 247 58

1. Atrial natriuretic peptide (ANP) (10(-9) to 10(-8) M) produced a concentration-related relaxation in helical strips of dog cerebral arteries partially contracted with prostaglandin F2 alpha. The relaxation was not affected by treatment with ouabain, quinidine, oxyhaemoglobin, methylene blue, or removal of endothelium. 2. Relaxations induced by nicotine or transmural electrical stimulation were not reduced in arteries in which tachyphylaxis to ANP had developed. 3. In arteries exposed to Ca2+-free media under severe hypoxia, contractions due to prostaglandin F2 alpha and Ca2+ were attenuated by treatment with ANP, whereas the reoxygenation-induced contraction was unaffected. 4. The results suggest that ANP does not mediate neurogenic relaxation of dog cerebral arteries. The ANP-induced relaxation is not associated with activation of the sodium pump but is due to an inhibitory action on the release and influx of Ca2+, probably as a result of stimulation of guanylate cyclase.
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PMID:Action of atrial natriuretic peptide (ANP) on dog cerebral arteries: evidence that neurogenic relaxation is not mediated by release of ANP. 252 17

The discovery of atrial natriuretic factor (ANF) constitutes a major advance in our knowledge of negative cell regulatory pathways leading to vasodilation. The biochemical mechanisms of the action of ANF at the cellular level appear to be mediated by the cGMP- particulate guanylate cyclase system. In the kidney, the main cGMP increasing effect of ANF occurs at the level of the glomeruli, but it appears that action of ANF at the lowest part of the distal tubule is required for its natriuretic activity. Although most current knowledge concerning ANF has been obtained with pharmacological doses of the hormone, it appears that endogenous manipulations of ANF, such as those occurring with postural change, are associated with physiological consequences including increases of cGMP, natriuresis, and diuresis. In both experimental and human hypertension, increased plasma levels of ANF are secondary to higher blood pressure. In hypertension, the administration of ANF leads to an exaggerated renal response. We propose as a hypothesis that an abnormality in the expression of a vasodilatory system, such as ANF-cGMP, may play a role in the pathogenesis of hypertension.
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PMID:Atrial natriuretic factor, the kidney and high blood pressure. 253 87

The hypotensive, natriuretic, and diuretic actions of human atrial natriuretic factor-(99-126) (hANF) are accompanied by an elevation of cyclic guanosine monophosphate (cGMP) in plasma and urine. However, the oxidized hANF analogue, human [Met-O110]ANF-(99-126) (Met-O-ANF), has been reported to be unable to increase cGMP (Biochem. Biophys. Res. Commun. 128: 538-546). We employed this oxidized peptide to evaluate the relationship between its biological effects and cGMP generation, with cGMP serving as a marker of the recognized property of ANF to stimulate particulate guanylate cyclase. Met-O-ANF appeared to be a partial agonist, exhibiting a decreasing order of relative potency of hypotensive, vasorelaxant, diuretic, and natriuretic functions compared to hANF. A lower degree of cGMP increases was achieved by this analogue in cultured smooth muscle and endothelial cells. Met-O-ANF doses, which led to a significant increase in diuresis, were neither natriuretic nor accompanied by an increase of urinary cGMP. We were thus able to dissociate the diuretic and natriuretic effects of ANF. High doses of the oxidized analogue were required to elevate cGMP levels in plasma and urine. In isolated kidney fractions, Met-O-ANF's action on cGMP was significantly lower in glomeruli (fivefold less), virtually absent in the collecting duct, yet only slightly different (20% less) in thick ascending limb. Our results indicate that the diuretic and natriuretic effects are exerted at distinct sites, with only the natriuresis being related to an increase of extracellular cGMP. The variability of differential potency of biological and biochemical effects from tissue to tissue of these two forms of human ANF support the notion of the heterogeneity of the ANF effector system.
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PMID:Dissociation of natriuresis and diuresis and heterogeneity of the effector system of atrial natriuretic factor in rats. 253 99


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