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)

Elevated concentrations of atrial natriuretic peptide reportedly mitigate acute renal failure in vivo and in the isolated perfused kidney (M. Nakamoto, J.I. Shapiro, P.F. Shanley, L. Chan & R.W. Shrier (1987) J. Clin. Invest. 80, 698-705; S.G. Shaw, J. Weidmann, J. Hodler, A. Zimmermann & A. Paternostro (1987) J. Clin. Invest. 80, 1232-1237). Since atrial natriuretic peptide has been shown to be a potent vasodilator, this beneficial effect may be due entirely to improved haemodynamics. To determine whether atrial natriuretic peptide also has a protective effect at the cellular level, rat hepatocyte cell cultures were treated with atrial natriuretic peptide prior to or after induction of cell damage by hypoxia (0.5% O2 for 4 h) or reactive oxygen (hypochlorous acid). Bleb formation, degradation of radiolabeled trichloroacetic acid-precipitable peptides, release of lactate dehydrogenase and trypan blue exclusion were used as indicators of cell damage. Atrial natriuretic peptide treatment distinctly protected the cell cultures against damage in both cases. This beneficial effect of atrial natriuretic peptide was partly mimicked by sodium nitroprusside, which, like atrial natriuretic peptide, largely increased the cellular cGMP content. 6-Anilino-5,8-quinolinedione (Ly 83583), an inhibitor of particulate guanylate cyclase, blocked the protective effect of atrial natriuretic peptide. Therefore a cGMP-mediated mechanism seems to be involved in the cytoprotective action of atrial natriuretic peptide. Fluorometric measurements using the Ca2+-sensitive dye Quin-2 showed that the elevation of intracellular Ca2+ after cellular insult by hypochlorous acid is prevented by atrial natriuretic peptide. These results suggest that atrial natriuretic peptide may attenuate hypoxic and toxic cell damage by increasing cGMP and reducing intracellular Ca2+.
J Clin Chem Clin Biochem 1989 Sep
PMID:Atrial natriuretic peptide protects hepatocytes against damage induced by hypoxia and reactive oxygen. Possible role of intracellular free ionized calcium. 255 49

Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.
Nature 1989 Sep 07
PMID:Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases. 257 Mar 58

Atrial natriuretic peptide (ANP) binds directly to a plasma membrane form of guanylate cyclase (GC-A), stimulating the production of the second messenger cyclic GMP. We show that a second guanylate cyclase/receptor (GC-B) exists, with distinctly different specificities for various natriuretic peptides. A cDNA clone encoding GC-B was isolated by low-stringency screening of a rat brain cDNA library using GC-A cDNA as a probe. The deduced amino acid sequence of GC-B is 78% identical with GC-A within the intracellular region, but 43% identical within the extracellular domain. Cyclic GMP concentrations in cells transfected with GC-A were half-maximally elevated at 3 nM ANP, 25 nM brain natriuretic peptide (BNP), and 65 nM atriopeptin 1, while 25 microM ANP, 6 microM BNP, and greater than 100 microM atriopeptin 1 were required for half-maximal stimulation of GC-B. The potencies of natriuretic peptides on GC-A and GC-B activity are therefore markedly different; furthermore, despite the specificity of GC-B for BNP, the relatively high BNP concentration required to elicit a response suggests the possible presence of a more potent, unidentified natural ligand.
Cell 1989 Sep 22
PMID:The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. 257 Jun 41

A plasma membrane form of guanylate cyclase is a cell surface receptor for atrial natriuretic peptide (ANP). In response to ANP binding, the receptor-enzyme produces increased amounts of the second messenger, guanosine 3',5'-monophosphate. Maximal activation of the cyclase requires the presence of adenosine 5'-triphosphate (ATP) or nonhydrolyzable ATP analogs. The intracellular region of the receptor contains at least two domains with homology to other proteins, one possessing sequence similarity to protein kinase catalytic domains, the other to regions of unknown function in a cytoplasmic form of guanylate cyclase and in adenylate cyclase. It is now shown that the protein kinase-like domain functions as a regulatory element and that the second domain possesses catalytic activity. When the kinase-like domain was removed by deletion mutagenesis, the resulting ANP receptor retained guanylate cyclase activity, but this activity was independent of ANP and its stimulation by ATP was markedly reduced. A model for signal transduction is suggested in which binding of ANP to the extracellular domain of its receptor initiates a conformational change in the protein kinase-like domain, resulting in derepression of guanylate cyclase activity.
Science 1989 Sep 22
PMID:The protein kinase domain of the ANP receptor is required for signaling. 257 Nov 88

The effect of water deprivation and salt loading on rat atrial natriuretic peptide (99-126) (rANP)-stimulated guanylate cyclase activity was investigated in the rat subfornical organ. rANP stimulated the formation of cGMP in rat subfornical organ crude homogenates in a dose- and time-dependent manner. An elevated responsiveness to rANP-induced cGMP production was observed in the subfornical organ after 4 days of water deprivation; on the contrary, after salt loading the response to the cGMP-generating effects of ANP were less pronounced than those in the corresponding control tissue. Our results suggest that cGMP mediates at least some of the central actions of rANP through the activation of specific receptors in localized target sites, and they provide evidence suggesting that the guanylate cyclase-coupled ANP-binding sites are susceptible to the regulatory mechanism described in the rat subfornical organ.
Neuroendocrinology 1989 Sep
PMID:Effect of water deprivation and salt loading on atrial natriuretic peptide-stimulated guanylate cyclase activity in the rat subfornical organ. 257 54

Since atrial natriuretic factor (ANF) is a natriuretic and vasodilatory hormone, its mechanisms of action expectedly involve so-called negative pathways of cell stimulation, notably cyclic nucleotides. Indeed, the guanylate cyclase-cyclic GMP (cGMP) system appears to be the principal mediator of ANF's action. Specifically, particulate guanylate cyclase, a membrane glycoprotein, transmits ANF's effects, as opposed to the activation of soluble guanylate cyclase such agents as sodium nitroprusside. The stimulation of particulate guanylate cyclase by ANF manifests several characteristics. One of them is the functional irreversibility of stimulation with its apparent physiological consequences: the extended impact of ANF on diuresis and vasodilation in vivo lasts beyond the duration of increased plasma ANF levels and is accompanied by a prolonged elevation of cGMP. Another characteristic is the parallelism between guanylate cyclase stimulation and increases of cGMP in extracellular fluids. cGMP egression appears to be an active process, yet its physiological implications remain to be uncovered. In heart failure, cGMP continues to reflect augmented ANF levels, suggesting that in this disease, the lack of an ANF effect on sodium excretion is due to a defect distal to cGMP generation. In hypertension, where ANF levels are either normal or slightly elevated, probably secondary to high blood pressure, the ANF responsiveness of the particulate guanylate cyclase-cGMP system, the hypotensive effects, diuresis and natriuresis are exaggerated. The implications of this exaggerated responsiveness of the ANF-cGMP system in the pathophysiology of hypertension and its potential therapeutic connotations remain to be evaluated.
Can J Physiol Pharmacol 1989 Sep
PMID:Biochemical mechanisms of atrial natriuretic factor action. 257 29

Elevation of cyclic GMP by muscarinic agonists has been suggested to be responsible for the negative inotropic effects of these agents in cardiac muscle, and for the endothelium-dependent relaxation caused by these agents in vascular smooth muscle. These relationships were studied by monitoring the effects of muscarinic agonists on tension and cyclic GMP levels in rabbit left atrial strips and aortic rings, in the presence and absence of the cyclic GMP lowering agent, LY83583. LY83583 completely blocked both the cyclic GMP increase and the relaxation caused by acetylcholine in rabbit aortic rings with intact endothelial cells. Acetylcholine-induced cyclic GMP elevation and relaxation in these preparations were also blocked by quinacrine and nordihydroguaiaretic acid (NDGA), but neither response was blocked by the 5-lipoxygenase inhibitor U-60257. In the experiments with rabbit left atrium, LY83583 blocked the acetylcholine-induced cyclic GMP elevation but did not block the negative inotropic effects of the drug. Quinacrine, NDGA, and a guanylate cyclase inhibitor, methylene blue, failed to block either the cyclic GMP increase or the decrease in contractile force caused by carbachol in atrial strips. These results support the suggestion that an increase in cyclic GMP may be responsible for the endothelium-dependent relaxation of rabbit aorta by muscarinic agonists, but not for the direct negative inotropic effects of these drugs in rabbit atrium. Muscarinic agents appear to increase cyclic GMP levels in rabbit atrium and aorta by different mechanisms. Although both are blocked by LY83583, they differ not only in their requirements for endothelial cells, but also in their susceptibility to other blocking agents.
Can J Physiol Pharmacol 1987 Sep
PMID:Effects of LY83583, nordihydroguaiaretic acid, and quinacrine on cyclic GMP elevation and inhibition of tension by muscarinic agonists in rabbit aorta and left atrium. 282 46

Atrial natriuretic factor (ANF) is actively involved in the control of blood pressure and fluid homeostasis as a physiological antagonist of the renin-angiotensin system. To evaluate a possible interaction between ANF and angiotensin II (Ang-II) receptors, we investigated the effect of long term pretreatment (18 h) of rat cultured vascular smooth muscle cells with Ang-II. Binding of 125I-labeled ANF and cyclic GMP production induced by ANF were measured. After preincubation of the cells with Ang-II (1, 10, and 100 nM), the number of ANF binding sites (Bmax) was decreased by 30, 59, and 71%, respectively, with a slight decrease of the Kd values. Sar1-Ile8-Ang-II (100 nM), a specific Ang-II receptor antagonist, totally inhibited the down-regulation induced by Ang-II (10 nM). Moreover, the regulatory effect of Ang-II on ANF receptors appeared more slowly as compared to ANF homologous receptor regulation. Ang-II pretreatment did not desensitize but increased cyclic GMP production elicited by ANF, implying that only the number of non-guanylate cyclase-coupled receptors was affected. These findings, which were not observed with 100 nM of epinephrine, norepinephrine, histamine, serotonin, and Arg-vasopressin, demonstrate a specific and functional link between ANF and Ang-II receptors. This study also shows that the regulation of ANF receptors is heterogeneous, providing new evidence of multiple classes of ANF receptors.
J Biol Chem 1988 Sep 15
PMID:Regulation of atrial natriuretic factor receptors by angiotensin II in rat vascular smooth muscle cells. 284 14

A novel type of monoclonal antibodies against cyclic GMP were produced to study the immunocytochemical distribution of cyclic GMP in the rat brain. Cyclic GMP conjugated to bovine serum albumin with glutaraldehyde was used as an immunogen, and monoclonal antibodies were produced. The one monoclonal antibody which did not crossreact against other nucleotides was applied to the immunocytochemistry of the rat brain. Cyclic GMP immunoreactivities were distributed unevenly in the rat brain. The cerebellar cortex, hippocampus and cerebral cortex contained a high degree of cyclic GMP immunoreactivity, while most of the white matter was not stained. In the cerebellar cortex, stellate cells and Golgi cells showed intense immunoreactivities, but granule cells showed weak immunoreactivities. Approximately 60-80% of the Purkinje cells showed intense immunoreactivities, while the remaining ones showed only weak staining. The pyramidal cells in the cerebral cortex and hippocampus also showed intense immunostaining. Some glial cells adjacent to the Purkinje cells also stained. The nuclei of cyclic GMP-immunoreactive cells were not stained. These immunocytochemical distributions of cyclic GMP are in fairly good agreement with reported the biochemical data and the immunocytochemical distribution of guanylate cyclase. These monoclonal antibodies should be helpful for elucidating the physiological role of cyclic GMP in the brain.
Jpn J Pharmacol 1988 Sep
PMID:Novel type of monoclonal antibodies against cyclic GMP and application to immunocytochemistry of the rat brain. 284 63

A 23 amino acid synthetic peptide fragment of atrial natriuretic factor (ANF) stimulated guanylate cyclase activity in isolated human glomeruli in a concentration- and time-dependent manner. ANF activated particulate guanylate cyclase whereas it had no effect on soluble guanylate cyclase. These results demonstrate that the glomerulus is a target structure for ANF in humans. They also suggest that ANF-induced increase in glomerular filtration rate is due to a direct effect of this peptide on the glomerular cells mediated by activation of glomerular guanylate cyclase.
FEBS Lett 1985 Sep 09
PMID:Stimulation of guanylate cyclase by atrial natriuretic factor in isolated human glomeruli. 286 74


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