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)

Extracts of mammalian atria, but not ventricles, induce marked diuresis, natriuresis, and reduction in blood pressure when infused systemically in rats and dogs. These extracts also inhibit aldosterone biosynthesis and renal renin release. Natriuretic peptides, 21 amino acids and longer, have been isolated from atria of rodents and man, and share a nearly homologous amino acid sequence at the carboxyterminus. Natriuretic activity resides in a 17-amino acid ring formed by a disulfide bridge, and the C-terminal Phe-Arg appears necessary for full biological potency. The deoxyribonucleic acid-encoding atrial natriuretic peptides have been cloned and the gene structure elucidated. Reduction of the diuretic and natriuretic responses to an acute volume load by right atrial appendectomy first suggested a role for atrial peptides in the physiological response to plasma volume expansion. Subsequently, release of peptides with natriuretic and spasmolytic properties from isolated heart preparations in response to right atrial distension was demonstrated by bioassay and radioimmunoassay. The presence of these peptides in normal rat and human plasma in concentrations of 20-100 pM, and the findings of increased levels in response to acute and chronic plasma volume expansion, rapid atrial tachyarrhythmias, systemic hypertension, congestive heart failure, and renal insufficiency imply that they play an important role in body fluid homeostasis. The mechanisms by which atrial peptides increase renal salt and water excretion are as yet unclear. Renal vascular effects have been consistently demonstrated, and limited evidence for direct actions on tubule ion transport has also been reported recently. In vitro, these peptides cause precontracted vascular and nonvascular smooth muscle to relax, mediated by a direct action on smooth muscle cells. Specific receptors for these peptides have been characterized in crude membranes prepared from whole kidney homogenates and adrenal glomerulosa cells, in intact glomeruli and cultured glomerular mesangial cells, and in intact bovine aortic smooth muscle and endothelial cells. Natriuretic peptides stimulate cyclic guanosine monophosphate accumulation in target tissues, and augment particulate guanylate cyclase activity in membrane fractions, suggesting that cyclic guanosine monophosphate is the second messenger mediating their cellular action.
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PMID:George E. Brown memorial lecture. Role of atrial peptides in body fluid homeostasis. 301 7

Effects of clonidine and yohimbine on plasma cyclic nucleotide levels were investigated in both clonidine-naive and clonidine-treated male mice. Clonidine increased plasma cyclic GMP but decreased slightly cyclic AMP levels in clonidine-naive mice. Clonidine treatment for 10-14 days in the drinking water did not decrease the cyclic GMP response to clonidine indicating that no tolerance develops to the effect of clonidine on plasma cyclic GMP. alpha 2-Agonists, such as clonidine, oxymetazoline and naphazoline, were more potent than phenylephrine, an alpha 1-agonist, in increasing cyclic GMP, although azepexole, a weak alpha 2-agonist, had no effect. Inhibition of clonidine-induced increase in plasma cyclic GMP by yohimbine, hexamethonium and atropine, but not by prazosin suggests that the effect of clonidine is mediated by the central alpha 2-adrenoceptors, activating the muscarinic receptor-linked guanylate cyclase through the stimulation of vagal activity. Yohimbine increased plasma cyclic AMP levels in clonidine-naive mice. Inhibition of this effect by hexamethonium and propranolol suggests that yohimbine increases plasma cyclic AMP through increasing the sympathetic tone. The increase in plasma cyclic AMP elicited by yohimbine was potentiated by chronic clonidine treatment. Enhancement of the cyclic AMP effect of yohimbine found in clonidine-treated mice may be regarded as a precipitated withdrawal symptom and indicate development of dependence on clonidine.
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PMID:Effects of clonidine and yohimbine on plasma cyclic nucleotide levels in clonidine-naive and clonidine-treated mice. 301 8

Two independent series of biomedical investigations have led to the discovery that the atria are a peptide-secreting endocrine gland. The first is mainly morphological and starts with the finding that mammalian atrial but not ventricular cardiocytes contain "dense bodies". These "dense bodies" later called "specific granules" were found to be different from lysosomes, to be made up of proteins and to incorporate both 3H-leucine and 3-H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than 4 years, this new natriuretic hormone has been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The ANF gene has been assigned to the distal short arm of chromosome 1 in band 1P36 while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure and expansion of blood volume are already beginning to emerge. On the other hand, the search for natriuretic hormones or factors by studies of negative pressure breathing, atrial distention experiments, head-out water immersion, expansion of blood volume, Na+/K-ATPase inhibition and parabiosis experiments in Dahl rats has provided a general framework within which to interpret this new cardiac function.
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PMID:[The heart, an endocrine gland]. 301 75

Two independent series of biomedical investigations have led to the discovery that the atria constitute a peptide-secreting endocrine gland. The first investigation is mainly morphological and started with the finding that mammalian atrial (but not ventricular) cardiocytes contain "dense bodies." These "dense bodies," later called "specific granules," were found to be different from lysosomes; to be made up of proteins; and to incorporate both 3H-leucine and 3H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than five years, this new natriuretic hormone has been purified, sequenced and synthesized, and its CDNA and gene have been cloned. The atrial natriuretic factor (ANF) gene has been assigned to the distal short arm of chromosome 1 in band 1P36, while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are already beginning to emerge. Concurrently, the search for the function of natriuretic hormones or factors (through studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibition, and parabiosis experiments in Dahl rats) has provided a general framework within which to interpret this new cardiac function.
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PMID:The heart as an endocrine gland. 302 9

Previous studies have suggested that (1) nitroglycerin causes vasodilatation by interacting with sulfhydryl groups in vascular smooth muscle, thereby activating guanylate cyclase and increasing the intracellular concentration of cyclic GMP, and (2) N-acetylcysteine, a source of sulfhydryl groups, potentiates the peripheral vasodilatory effect of nitroglycerin. This study was performed to explore the influence of N-acetylcysteine on nitroglycerin-induced coronary dilatation. In 18 patients (13 men and five women, 30 to 76 years old), coronary sinus blood flow (by thermodilution) was measured before and during intracoronary administration of nitroglycerin, 25 micrograms, both before and 5 min after a 15 min intravenous infusion of (1) 5% dextrose in water (n = 8, control) or (2) 100 mg/kg N-acetylcysteine (n = 10). Nitroglycerin caused no change in heart rate or systemic arterial pressure. In the control patients, coronary sinus blood flow behaved similarly during the two injections: it was 134 +/- 36 ml/min (mean +/- SD) before and 183 +/- 50 ml/min during injection No. 1 (average increase, 49 +/- 25 ml/min; average percent increase, 38 +/- 21%); and it was 131 +/- 34 ml/min before and 178 +/- 45 ml/min during injection No. 2 (average increase, 47 +/- 23 ml/min; average percent increase, 37 +/- 20%) (NS compared with injection 1). In the patients who received N-acetylcysteine, coronary sinus blood flow was 149 +/- 48 ml/min before and 191 +/- 54 ml/min during injection 1 (average increase, 42 +/- 15 ml/min; average percent increase, 30 +/- 12%) (NS compared with eight control values).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Potentiation of nitroglycerin-induced coronary dilatation by N-acetylcysteine. 307 76

The enzyme guanylate cyclase is stimulated to produce cycle guanosine 3',5'-monophosphate (GMP) when lung tissue is exposed to cigarette smoke in vitro. These experiments tested whether in vivo exposure in rats to cigarette smoke produces a similar response. Adult rats were anaesthetized with pentobarbital and ventilation with mixtures of air and cigarette smoke at 10 cm H2O inspiratory pressure was achieved after a tracheotomy was performed. Lung tissue samples were taken at intervals during 20 min exposure period and analyzed for levels of cyclic adenosine 3', 5'-monophosphate (AMP) and cycle GMP. Blood carboxyhemoglobin (COHb) levels at 5 min and 15 min of exposure showed high, but sublethal levels of COHb. lung tissue cAMP was unchanged with this exposure, but cGMP levels rose dramatically. Rat lungs showed no changes related to ventilation under similar conditions in the absence of smoke. This observed response of cGMP to cigarette smoke may represent an important pulmonary defense mechanism.
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PMID:Cigarette smoke exposure in vivo increases cyclic GMP in rat lung. 625 86

The effect of parathyroid hormone (PTH) on jejunal sodium, calcium, and water transport in situ was studied in thyroparathyroidectomized rats using the ligated loop instillation model. The acute administration of bovine PTH to the animals induced a significant increase in net sodium and water secretion when compared to animals receiving the vehicle only. This effect was due to an increase in unidirectional mucosa-to-lumen sodium flux. However, no change of calcium fluxes was observed. This acute in vivo effect on PTH could not be explained by an action via the adenyl or guanyl cyclase systems since bPTH failed to induce changes of cAMP or cGMP formation in isolated jejunal cells. Thus, other so far not elucidated mechanisms of action must be involved.
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PMID:Effect of parathyroid hormone on jejunal electrolyte and water transport and cyclic nucleotide formation in the rat. 625 5

E. coli which elaborate suckling mouse active small MW heat-stable enterotoxin (STa), are important causes of diarrhea in animals and man. These STa's share the property of causing intestinal secretion and diarrhea by virtue of inhibiting the absorption of sodium and chloride and possibly stimulating the secretion of chloride. STa's seem to act in the colon as well as the small intestine and the alterations in intestinal ion and water transport are probably mediated by the guanylate cyclase-cyclic GMP system. Glucose transport is unaffected. STa also causes alterations in the myoelectrical activity of the small intestine which may result in the loss of normal peristaltic activity. STa binds in a reversible fashion to specific receptors on the surface of small intestinal and colonic epithelial cells. The mechanisms whereby occupation of the STa receptors lead to activation of the guanylate cyclase system and intestinal secretion are unknown but may involve influx of calcium through calcium channels, stimulation of prostaglandin synthesis and release of free radicals.
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PMID:Escherichia coli heat-stable enterotoxin: biochemical and physiological effects on the intestine. 668 36

Heat-stable enterotoxins (STa) produced by pathogenic bacteria induce profound salt and water secretion in the gut, leading to diarrhea. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. Here we show that STa, guanylin and cGMP each activate intestinal Cl- secretion, and that this is abolished by inhibitors of cAMP-dependent protein kinase (PKA), suggesting that PKA is a major mediator of this effect. These agents induce Cl- secretion only in cells expressing the wild-type CFTR, indicating that this molecule is the final common effector of the signaling pathway. The involvement of CFTR suggests a possible cystic fibrosis heterozygote advantage against STa-induced diarrhea.
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PMID:Activation of intestinal CFTR Cl- channel by heat-stable enterotoxin and guanylin via cAMP-dependent protein kinase. 751 Jun 34

As atrial natriuretic factor (ANF) is intimately involved in water and electrolyte homeostasis, dose-response studies were performed in the parotid as well as submaxillary glands of the rat with increasing doses of the atrial peptide to investigate its possible role as a sialogogic agent. Dose-response studies were also performed in both salivary glands with different pharmacological agonists known to cause salivation in the rat (methacholine, noradrenaline, isoproterenol, methoxamine and substance P) in the absence and in the presence of ANF. The atrial factor did not induce salivation 'per se' at least in the investigated doses. However, it enhanced the salivary response to methacholine, methoxamine and substance P but it did not modify the salivation induced either by noradrenaline or isoproterenol. The present results showed that ANF enhanced the salivation induced by pharmacological agents which stimulate phosphatidylinositol hydrolysis. These effects of ANF may be probably related to the activation of the non-guanylate cyclase coupled receptor which has been associated with phosphatidylinositol turnover. Nevertheless, although the atrial factor induces vasorelaxation, its enhancement of blood flow may not be the major event underlying the present results. The present work suggests a potential physiological role of ANF on the modulation of salivary secretion and provides further evidence on the rol of ANF in the regulation of body fluid homeostasis.
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PMID:Atrial natriuretic factor enhances induced salivary secretion in the rat. 751 Dec 49


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