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

In this study we used HS-142-1, a novel non-peptide antagonist for the atrial natriuretic peptide (ANP) receptor, to clarify the possible physiological significance of ANP in acute hypervolemia. Substantial volume expansion in anesthetized rats induced a strong diuresis and natriuresis. These renal responses were significantly blocked by HS-142-1 at a dose of 3.0 mgkg-1 i.v. This observation suggests that ANP and its guanylyl cyclase-coupled receptor are, under the present conditions, physiologically involved that appears to be responsible for the renal responses in the volume homeostasis.
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PMID:Effects of HS-142-1, a novel non-peptide ANP antagonist, on diuresis and natriuresis induced by acute volume expansion in anesthetized rats. 131 Mar 97

Atriopeptins are a recently-discovered group of polypeptides secreted from cardiac myocytes in response to fluid overload. The present studies demonstrate that atriopeptin receptors, coupled to the activation of guanylate cyclase, are present in rabbit ciliary process. Rat atrial natriuretic peptide 1-28 (rANP) activated ciliary process guanylate cyclase activity with a Vmax of from 24-337% and with a Ka of from 0.4-4 nM, similar to that for atriopeptin receptors present in rabbit kidney. Activation was greater for the intact peptide than for rANP fragments 1-11 or 13-28, and stimulated activity was greater in isolated ciliary processes than in ciliary muscle or iris. Intravitreal injection of the complete peptide into living rabbits caused a marked decrease in IOP in the ipsilateral eye which persisted for more than 48 hr and occurred without evidence of an inflammatory response. There was a smaller decrease in IOP in the contralateral eye. Following intravitreal injection of rANP 1-28, atriopeptin levels in aqueous humor remained elevated for at least 44 hr. Injection of the biochemically less active rANP fragments 1-11 and 13-28 caused no decrease in IOP. These physiological data, together with the biochemical identification of atriopeptin receptors and second messenger systems in the ciliary process, suggest that certain tissues of the anterior segment may be atriopeptin end-organs and that agents acting at atriopeptin receptors may be able to regulate IOP.
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PMID:Atriopeptin-activated guanylate cyclase in the anterior segment. Identification, localization, and effects of atriopeptins on IOP. 288 48

Increases in plasma cyclic GMP levels have been shown to correlate with increased plasma levels of atrial natriuretic peptide (ANP) in patients with fluid overload due to increased secretion of ANP. There is evidence that plasma cyclic GMP levels are also elevated in some patients with acute leukemia, but increased ANP secretion has not been demonstrated. To elucidate the possibility that a newly expressed guanylyl cyclase may be responsible for the increase of plasma cyclic GMP levels patients with acute and chronic leukemia as well as patients with lymphoma and healthy volunteers were studied. Plasma levels of cyclic GMP were measured and isolated peripheral blood mononuclear or bone marrow cells were incubated with increasing concentrations of ANP. The stimulation of cells was measured as cGMP accumulation in the supernatant. Furthermore guanylyl cyclase activity was measured in membrane preparations of peripheral blood mononuclear cells. While leukocytes of healthy subjects were devoid of detectable ANP-stimulated particulate guanylyl cyclase activity, ANP-sensitivity was observed in seven patients with acute lymphoblastic and in three patients with acute myelogenous leukemia. Cyclic GMP in the supernatant of cells was elevated between 2- and 132-fold of basal when cells were incubated with 1 microM ANP for 60 minutes. Like in healthy volunteers, no effect of ANP on freshly isolated mononuclear cells was observed in cases with chronic leukemia or in patients with lymphoma. Expression of ANP-sensitive particulate gunaylyl cyclase may be connected with malignant transformation of lymphocytes in patients with acute leukemia and might be useful for their diagnosis and classification.
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PMID:Particulate ANP-sensitive guanylyl cyclase in blood and bone marrow cells of patients with acute leukemia. 911 98

Natriuretic peptides exist in the fishes as a family of structurally-related isohormones including atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and ventricular natriuretic peptide (VNP); to date, brain natriuretic peptide (or B-type natriuretic peptide, BNP) has not been definitively identified in the fishes. Based on nucleotide and amino acid sequence similarity, the natriuretic peptide family of isohormones may have evolved from a neuromodulatory, CNP-like brain peptide. The primary sites of synthesis for the circulating hormones are the heart and brain; additional extracardiac and extracranial sites, including the intestine, synthesize and release natriuretic peptides locally for paracrine regulation of various physiological functions. Membrane-bound, guanylyl cyclase-coupled natriuretic peptide receptors (A- and B-types) are generally implicated in mediating natriuretic peptide effects via the production of cyclic GMP as the intracellular messenger. C- and D-type natriuretic peptide receptors lacking the guanylyl cyclase domain may influence target cell function through G(i) protein-coupled inhibition of membrane adenylyl cyclase activity, and they likely also act as clearance receptors for circulating hormone. In the few systems examined using homologous or piscine reagents, differential receptor binding and tissue responsiveness to specific natriuretic peptide isohormones is demonstrated. Similar to their acute physiological effects in mammals, natriuretic peptides are vasorelaxant in all fishes examined. In contrast to mammals, where natriuretic peptides act through natriuresis and diuresis to bring about long-term reductions in blood volume and blood pressure, in fishes the primary action appears to be the extrusion of excess salt at the gills and rectal gland, and the limiting of drinking-coupled salt uptake by the alimentary system. In teleosts, both hypernatremia and hypervolemia are effective stimuli for cardiac secretion of natriuretic peptides; in the elasmobranchs, hypervolemia is the predominant physiological stimulus for secretion. Natriuretic peptides may be seawater-adapting hormones with appropriate target organs including the gills, rectal gland, kidney, and intestine, with each regulated via, predominantly, either A- or B-type (or C- or D-type?) natriuretic peptide receptors. Natriuretic peptides act both directly on ion-transporting cells of osmoregulatory tissues, and indirectly through increased vascular flow to osmoregulatory tissues, through inhibition of drinking, and through effects on other endocrine systems.
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PMID:Natriuretic peptides in fish physiology. 1082 90

To clarify whether exercise-training affects ANP function, we trained male Wistar rats by treadmill running for nine weeks and measured ANP receptor number and affinity in the kidney, lung and adrenal. We also measured guanylate cyclase activity, by which second messenger cGMP accumulates. The number of adrenal ANP receptor significantly increased after exercise-training. There was no significant difference of affinity for all the organs examined between the training group and the control group. Guanylate cyclase activity tended to decrease in the kidney in the training group. A significant difference was found when the samples were stimulated by C-type natriuretic peptide (CNP). There was no significant difference in guanylate cyclase activity in the lung and adrenal. These findings are consistent with the exercise-induced hypervolemia, but not with the anti-hypertensive role of exercise-training.
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PMID:Effect of exercise training on ANP receptors. 1191 14

After a salty meal, stimulation of salt excretion via the kidney is a possible mechanism to prevent hypernatremia and hypervolemia. Besides the well known hormonal regulators of salt and water excretion in the distal nephron, arginine vasopressin and aldosterone, guanylin (GN) peptides produced in the intestine were proposed to be intestinal natriuretic peptides. These peptides inhibit Na+ absorption in the intestine and induce natriuresis, kaliuresis and diuresis in the kidney. The signaling pathway of GN peptides in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C) and increase the cellular concentration of cGMP which leads to secretion of Cl-, HCO3- and water into the intestinal lumen and to inhibition of Na+ absorption. Guanylin peptides are filtered in the glomerulus, and additionally synthesized and excreted by tubular cells. They activate receptors located in the luminal membrane of the tubular cells along the nephron. In GC-C deficient mice renal effects of GN peptides are retained. In human, rat, and opossum proximal tubule cells, a cGMP-dependent signaling was demonstrated, but in addition GN peptides apparently also activate a PT-sensitive G-protein coupled receptor. A similar dual signaling pathway is also known for other natriuretic peptides like atrial natriuretic peptide. A cGMP-independent signaling pathway of GN peptides is also shown for principal cells of the human cortical collecting duct where the final hormonal regulation of electrolyte homeostasis takes place. This review will focus on the current knowledge on renal actions of GN peptides and specifically address novel GC-C- and cGMP-independent signaling mechanisms.
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PMID:Mechanisms of actions of guanylin peptides in the kidney. 1595 32

Ingestion of a salty meal induces secretion of guanylin (GN) and uroguanylin (UGN) into the intestinal lumen, where they inhibit Na+ absorption and induce Cl-, HCO3-, and water secretion. Simultaneously, these hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis. GN and UGN therefore participate in the prevention of hypernatremia and hypervolemia after salty meals. The signaling pathway of GN and UGN in the intestine is well known. They activate enterocytes via guanylate cyclase C (GC-C), which leads to cGMP-dependent inhibition of Na+/H+ exchange and activation of the cystic fibrosis transmembrane regulator. In GC-C-deficient mice, GN and UGN still produce renal natriuresis, kaliuresis, and diuresis, suggesting different signaling pathways in the kidney compared with the intestine. Signaling pathways for GN and UGN in the kidney differ along the various nephron segments. In proximal tubule cells, a cGMP- and GC-C-dependent signaling was demonstrated for both peptides. In addition, UGN activates a pertussis toxin-sensitive G-protein-coupled receptor. A similar dual signaling pathway is also known for atrial natriuretic peptide. Recently, a cGMP-independent signaling pathway for GN and UGN was also shown in principal cells of the human and mouse cortical collecting duct. Because GN and UGN activate different signaling pathways in specific organs and even within the kidney, this review focuses on more recent findings on cellular effects and signaling mechanisms of these peptides and their pathophysiologic implications in the intestine and the kidney.
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PMID:Cellular effects of guanylin and uroguanylin. 1638 16

Guanylin peptides (GPs) family includes guanylin (GN), uroguanylin (UGN), lymphoguanylin, and recently discovered renoguanylin. This growing family is proposed to be intestinal natriuretic peptides. After ingestion of a salty meal, GN and UGN are secreted into the intestinal lumen, where they inhibit sodium absorption and induce anion and water secretion. At the same conditions, those hormones stimulate renal electrolyte excretion by inducing natriuresis, kaliuresis, and diuresis and therefore prevent hypernatremia and hypervolemia after salty meals. In the intestine, a well-known receptor for GPs is guanylate cyclase C (GC-C) whose activation increases intracellular concentration of cGMP. However, in the kidney of GC-C-deficient mice, effects of GPs are unaltered, which could be by new cGMP-independent signaling pathway (G-protein-coupled receptor). This is not unusual as atrial natriuretic peptide also activates two different types of receptors: guanylate cylcase A and clearance receptor which is also G-protein coupled receptor. Physiological role of GPs in other organs (liver, pancreas, lung, sweat glands, and male reproductive system) needs to be discovered. However, it is known that they are involved in pathological conditions like cystic fibrosis, asthma, intestinal tumors, kidney and heart failure, obesity, and metabolic syndrome.
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PMID:Current understanding of guanylin peptides actions. 2496 39

We analyzed the contribution of soluble guanylate cyclase-dependent pathway into NO-mediated relaxation of pulmonary arteries under conditions of high pulmonary blood flow modeled by creation of carotid artery-jugular vein shunt in rats. Inhibitor of soluble guanylate cyclase suppressed NO-donor induced relaxation was lower in rats with shunt, but dilatation in response to phosphodiesterase V inhibitor did not differ in the sham-operated and shunt groups. Thus, the structure of NO-mediated vasodilatation of pulmonary arteries under conditions of hypervolemia of pulmonary circulation was shifted to soluble guanylate cyclase-independent pathways, whereas intracellular soluble guanylate cyclase-dependent mechanisms of dilatation were in general unchanged.
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PMID:Modeling of Hypervolemia in Pulmonary Circulation in Rats Changes the Structure of NO-Mediated Relaxation of Pulmonary Arteries. 3274 39