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)

We examined receptor binding profiles of atrial natriuretic peptide (ANP) in rat tissue using 125I-labeled alpha-rat ANP [( 125I]alpha-rANP). Specific [125I]alpha-rANP binding to its receptor was reversible following addition of unlabeled free alpha-rANP, but it became increasingly irreversible with time during incubation. Irreversible binding of alpha-rANP was observed both at 0 degrees and 25 degrees in homogenates of adrenal capsules and lungs, crude membranes of renal glomeruli, partially purified membranes of lung, solubilized membrane preparations from renal glomeruli, and intact renal glomeruli. Irreversible binding increased in a time- and temperature-dependent manner. HPLC analysis demonstrated that the irreversibly bound radioactivity, which was extracted by 1 N CH3COOH from both intact renal glomeruli and from partially purified membranes, was associated with intact [125I]alpha-rANP. Irreversibly bound alpha-rANP increased cGMP concentrations by activating guanylate cyclase activity. These findings suggest that the appearance of irreversible binding of alpha-rANP to its receptor is independent of its internalization, and may be involved in message transduction and subsequent biological responses.
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PMID:Stimulation of guanylate cyclase activity by irreversible binding of atrial natriuretic peptide to its receptor. 245 66

Chondroprogenitor cells derived from avian tibia epiphyseal growth plate, and skin fibroblasts were cultured in vitro. In the fibroblasts, human (1-28) and rat (5-28) atrial natriuretic peptide (ANP) stimulated cyclic GMP (cGMP) production in a dose-dependent manner without affecting cAMP. Sodium nitroprusside also stimulated cGMP accumulation by chondroprogenitor cells and fibroblasts, but the maximum cGMP accumulation elicited by sodium nitroprusside was much lower than that obtained with ANP. The effects of ANP and sodium nitroprusside on chondroprogenitor cells and skin fibroblasts were additive. Human ANP increased cGMP production by the particulate fraction prepared either from chondroprogenitor cells or fibroblasts. Sodium nitroprusside, at concentrations of up to 1 mmol/l, did not affect cGMP production by the particulate fraction prepared from either cell type. The present study provides additional evidence that avian growth-plate chondroprogenitor cells and skin fibroblasts are targets for ANP. ANP and nitroprusside activate different guanylate cyclase isoenzymes--the particulate and soluble forms of the enzyme respectively. The data suggest that most of the guanylate cyclase activity in these cells is localized in the particulate fraction.
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PMID:Atrial natriuretic peptide and sodium nitroprusside stimulate cyclic GMP accumulation by avian skin fibroblasts and epiphyseal growth-plate chondroprogenitor cells. 246 31

Several classes of vasodilators have been demonstrated to elicit their affects by activating guanylate cyclase and elevating intracellular concentrations of cyclic GMP. The nitrovasodilators, such as nitroglycerin, generate nitric oxide, which directly activates the soluble isoenzyme of guanylate cyclase resulting in increased intracellular concentrations of cyclic GMP. A second class of agents, the endothelium-dependent vasodilators, such as acetylcholine, requires an intact endothelium to elicit vascular smooth muscle relaxation, in contrast to the nitrovasodilators. These agents stimulate the release of an endothelium-derived relaxing factor (EDRF), which also activates the soluble form of guanylate cyclase, triggering the production of cyclic GMP. The third class of agents includes atrial natriuretic peptides (ANPs). These low-molecular-weight, heat-stable peptides bind to specific receptors on vascular smooth muscle. These receptors appear unique in that they have a dual function possessing both ANP binding and particulate guanylate cyclase activities. Binding to and activation of particulate guanylate cyclase, in the absence of endothelium, results in the elevation of intracellular concentrations of cyclic GMP and relaxation.
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PMID:Biochemical mechanisms underlying vascular smooth muscle relaxation: the guanylate cyclase-cyclic GMP system. 246 67

A possible role of dopamine in the diuretic and natriuretic action of atrial natriuretic peptide (ANP) was evaluated in the rat. ANP was infused into the left renal artery of anesthetized rats whose kidneys were denervated. ANP both at 12 and 1.2 pmol/h caused immediate ipsilateral increases in urine volume (V), urine Na excretion (UNaV), and fractional excretion of Na (FENa). Ipsilateral glomerular filtration rate (GFR) and renal plasma flow (RPF) increased with 12 pmol/h ANP but not with 1.2 pmol/h ANP. Intravenous infusion of haloperidol, Sch-23390, or carbidopa markedly attenuated the increase in V, UNaV, and FENa with 12 pmol/h ANP and completely abolished the increases in GFR and RPF. Haloperidol, Sch-23390, and carbidopa also completely abolished the renal effects of 1.2 pmol/h ANP. In the presence of carbidopa, a small dose of dopamine infused into the systemic circulation, which by itself has no effects on blood pressure, V, GFR, RPF, and UNaV, restored the diuretic and natriuretic effects of ANP. In addition, an increase in urinary guanosine 3',5'-cyclic monophosphate by ANP was not affected by either haloperidol or carbidopa. These data indicate that dopamine may be necessary, as a permissive agent, for the renal effects of ANP to manifest and that the effects of dopamine may be independent of ANP-stimulated guanylate cyclase activation.
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PMID:Permissive role of dopamine in renal action of ANP in volume-expanded rats. 252 70

The role of atrial natriuretic peptide to modulate the renal tubuloglomerular feedback response was examined in the dehydrated anesthetized dog using an infusion of hypertonic sodium chloride to increase renal plasma sodium concentration by 30 mEq/l as the stimulus to activate the tubuloglomerular feedback. Two sequential infusions of hypertonic sodium chloride into the renal artery for 10 min were separated by 90 min, and various interventions were introduced before the second hypertonic saline infusion. In the first group of dogs, the first infusion of hypertonic saline resulted in a significant decrease in renal blood flow from 234 +/- 36 to 199 +/- 31 ml/min, but when atriopeptin III (APIII) was infused into the renal artery at 3 x 10(-10) mol/min, the repeat infusion of hypertonic saline resulted in a significant increase in blood flow from 221 +/- 28 to 269 +/- 35 ml/min that was maintained throughout the 10 min of hypertonic saline. In the second group of dogs only the vehicle for APIII was infused during the second hypertonic saline infusion. In these dogs, renal blood flow decreased significantly the first time from 201 +/- 17 to 170 +/- 16 ml/min, and the second time from 232 +/- 22 to 177 +/- 20 ml/min. In a third group of dogs, the vasodilator sodium nitroprusside, a stimulator of smooth muscle soluble guanylate cyclase, was infused into the renal artery during the second hypertonic saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide blocks the renal vasoconstrictor response to hypertonic saline in the dog. 252 68

1. Aim. The biochemical characteristics of atrial natriuretic peptide receptors (ANP-R) derived from rat vascular smooth muscle (A-10 cell line) and central nervous system (CNS; olfactory bulb) tissue were compared. 2. Method and Results. ANP-Rs from each source were solubilized with 40 to 65% efficiency utilizing the nonionic detergent Lubrol-PX. Upon solubilization, the ANP-R from each source maintained the ability to bind 125I-ANP (99-126) with a high affinity; Scatchard analysis indicated that the VSMC ANP-R displayed a Kd for the radioligand of approximately 10 pM, whereas the olfactory receptor possessed a Kd of about 165 pM. The Bmax values for the soluble VSMC and olfactory ANP-Rs were 285 and 30 fmol/mg protein, respectively. Competition binding studies indicated that the VSMC ANP-R bound ANP(99-126), ANP(103-126), and ANP(103-123) with similar affinities, whereas the olfactory ANP-R was much more sensitive to changes in the COOH-terminal structure of the competing peptide. The soluble ANP-Rs from VSMC and olfactory were chromatographically indistinguishable on phenyl-, DEAE-, and wheat germ agglutinin-agarose columns. However, the ANP-Rs could be distinguished using GTP-agarose; the olfactory ANP-R was capable of binding to the resin, whereas the VSMC ANP-R was not. 3. Conclusions. Coupled with other studies, these data suggest that the A10 VSMC ANP-R observed in this study may not be coupled to guanylate cyclase and may represent a receptor serving a clearance function, whereas a significant proportion of the olfactory CNS ANP-R appears to be associated with GTP-binding proteins, likely particulate guanylate cyclase, and probably represents a coupled form of the receptor.
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PMID:Biochemical studies of soluble atrial natriuretic peptide (ANP) receptors from rat olfactory bulb and vascular smooth muscle cells. 254 Sep 12

1. Receptors for atrial natriuretic peptide (ANP) have been identified on mouse astrocytes in primary culture, and have similar characteristics to those found on previously recognized ANP-target tissues. 2. Scatchard analysis revealed one class of high affinity receptors with a Kd of 0.32 nmol/L. The IC50 for specific binding was 0.5 nmol/L. 3. Ligand binding resulted in stimulation of guanylate cyclase. 4. Under reducing conditions, the covalently cross-linked receptor-ANP complex migrated on SDS-polyacrylamide gels as a single band with an apparent molecular weight of 66 kDa. 5. Although the physiological relevance of our observations remains to be determined, these data document that cultured mouse astrocytes contain specific high-affinity ANP receptors which are linked to the production of cGMP.
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PMID:Mouse astrocytes possess specific ANP receptors which are linked to cGMP production. 254 96

We have investigated the role of Ca2+ and calmodulin in the stimulation of cGMP formation by mouse Leydig cells in response to rat atriopeptin-II (rAP-II). Removal of extracellular Ca2+ had no influence on the levels of cGMP accumulated by the cells stimulated with rAP-II. The amounts of testosterone produced by unstimulated and rAP-II-stimulated cells were, however, reduced by 50% in the absence of Ca2+ from the incubation medium. Addition of ionomycin to the Leydig cells led to a dose-related inhibition of rAP-II-stimulated cGMP formation, but the basal cGMP level was not affected. These experiments were carried out in the presence of a phosphodiesterase inhibitor. The inhibitory effect of ionomycin was absolutely dependent upon the presence of Ca2+ in the medium. The guanylate cyclase activity required the presence of a cation, and Mn2+, Mg2+, or Ca2+ could function as the required cation. There was no direct inhibition of the cyclase activity by Ca2+ up to as high a concentration as 8 mM. Furthermore, three structurally unrelated calmodulin antagonists, W7, trifluoperazine, and calmidazolium, but not W5, caused a dose-related inhibition of rAP-II-stimulated cGMP accumulation by the cells. The inhibitory effect of calmodulin antagonists was not exerted directly at the level of guanylate cyclase activity, since the particulate enzyme was not inhibited by any of these drugs. We conclude, therefore, that extracellular Ca2+ is not essential for rAP-II-mediated stimulation of cGMP formation by mouse Leydig cells, at least under the short term incubation conditions used. An excessive ionophoretic influx of Ca2+ into the cells impairs the ability of rAP-II to stimulate cGMP formation. Therefore, it appears that a finely regulated level of intracellular Ca2+ is required for optimal activation of atrial natriuretic peptide-responsive guanylate cyclase in mouse Leydig cells, and calmodulin plays an important role in this process.
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PMID:The role of Ca2+ and calmodulin in the regulation of atrial natriuretic peptide-stimulated guanosine 3',5'-cyclic monophosphate accumulation by isolated mouse Leydig cells. 254 43

1. Acetylcholine (ACh)-induced relaxation of aortic strips with endothelium and production of cyclic GMP between streptozotocin-induced diabetic and age-matched control rats were compared. 2. The concentration-response curve for ACh-induced relaxation was shifted to the right in diabetic rats. IC50 values for ACh were 4.57 +/- 0.67 x 10(-8) M and 1.00 +/- 0.87 x 10(-7) M in aortic strips from age-matched control and diabetic rats, respectively (n = 6, P less than 0.05). 3. Relaxations produced by atrial natriuretic peptide (ANP) in diabetic aortae were similar to those in age-matched vessels. 4. Relaxations produced by sodium nitroprusside (SNP) in diabetic aortae were similar to those in age-matched vessels. 5. Basal levels of cyclic GMP and ACh-induced production of cyclic GMP were significantly decreased in diabetic rats. 6. These results suggest that functional changes in endothelium but not in guanylate cyclase activity in the aorta may occur in diabetes, and thus, spontaneous and ACh-induced formation of cyclic GMP may be decreased. This decrease in production of cyclic GMP may be responsible for the decreased response of the aorta to the relaxant effect of ACh.
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PMID:Impairment of endothelium-dependent relaxation and changes in levels of cyclic GMP in aorta from streptozotocin-induced diabetic rats. 254 80

The expression and regulation of atrial natriuretic peptide (ANP) receptor subtypes were examined in rat renal glomeruli and papillae. In glomeruli, approximately two-thirds of ANP binding sites represented guanylate cyclase-uncoupled ANP clearance receptors (ANPc) with a molecular mass of 64 kDa under reducing conditions. The remainder of glomerular ANP binding sites represented guanylate cyclase-coupled ANP receptors (ANPGC) with a molecular mass of 130 kDa. In rat papillae, only the 130-kDa ANPGC was expressed. In rats adapted to a low-salt diet, saline loading or acute ANP infusion resulted in a decrease in ANPC density, a difference that was not detected when glomeruli were first acidwashed to remove endogenous ANP, indicating that apparent regulation of ANPC reflected prior occupancy by endogenous ANP. Densities of glomerular ANPC and ANPGC were similar in spontaneously hypertensive rats (SHR) compared with those of the Wistar-Kyoto (WKY) controls. However, elimination of prior receptor occupancy revealed a significantly greater expression of glomerular ANPC in SHR compared with WKY rats, without significant differences in the density of the glomerular or papillary ANPGC subtype. The failure of the ANPGC subtype to be regulated may account for our previously reported findings that dietary salt intake does not affect glomerular ANP-stimulated guanosine-3',5'-cyclic monophosphate accumulation despite apparent regulation of ANP receptor density. Whether the increased expression of the ANPC subtype in SHR represents a primary defect or results from induction of ANP clearance receptor expression remains to be determined.
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PMID:Expression and regulation of ANP receptor subtypes in rat renal glomeruli and papillae. 255 35


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