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)

Cyclic AMP in Strongylocentrotus purpuratus sperm was elevated approximately 2-fold by theophylline or 1-methyl-3-isobutylxanthine. Factors released from sea urchin eggs (FRE) elevated sperm cyclic AMP by about 7-fold within 1 min, and the combination of FRE with theophylline increased sperm cyclic AMP up to 100-fold within 1 min. Cyclic GMP in sea urchin sperm was slightly elevated by theophylline, but was lowered by FRE. Cyclic GMP in sperm treated with FRE plus theophylline was not higher than in sperm treated with theophylline alone. The ability of FRE-containing sea water to increase sperm cyclic AMP in the presence of theophylline was altered only slightly if at all by boiling, but it was decreased by about 50% by dialysis and destroyed by ashing. Filtration of FRE on Sephadex G-50 columns yielded two peaks of cyclic AMP-elevating activity. One peak (peak I) was eluted at the column void volume, and the other (peak II) was retained by the column. The cyclic GMP-lowering activity was located in fractions approximately corresponding to peak I of cyclic AMP-elevating activity. Dialysis of FRE-containing sea water before its application to the G-50 column virtually eliminated peak II of the cyclic AMP-elevating activity. When the cyclic AMP-elevating activity in peak I was filtered on Bio Gel A-5m columns, it also migrated at or near the column void volume. Fractions corresponding to peak I contained material that inhibited both guanylate and adenylate cyclase activities in broken cell preparations of sperm and guanylate cyclase from rat lung. The inhibitory material was stable to boiling, non-dialyzable, and destroyed by ashing. Under a variety of conditions, FRE-containing sea water or cyclic AMP-elevating peaks I or II did not stimulate sperm adenylate cyclase activity in broken cell preparations.
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PMID:Effects of egg factors on cyclic nucleotide metabolism in sea urchin sperm. 0 75

Ethanol decreases hepatic protein and albumin synthesis, and inhibits pancreatic water, bicarbonate, and protein secretion. Since these actions of ethanol are opposite to those reported for secretin, cholecystokinin-pancreozymin, and pentagastrin which may be mediated through increases in cyclic GMP, it appeared possible that the inhibitory actions of ethanol might be mediated through inhibition of guanylate cyclase, the enzyme that catalyzes the production of cyclic GMP. Ethanol inhibited soluble preparations of guanylate cyclase from rat liver, pancreas, stomach, and ileum. Maximal inhibition was observed at 5.0 and 2.5 percent ethanol. The inhibitory effects of ethanol on the guanylate cyclase-cyclic GMP system of these tissues provide a possible explanation for some of the diverse effects of ethanol on these tissues.
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PMID:Ethanol-induced inhibition of guanylate cyclase in liver, pancreas, stomach and intestine. 1 94

When the crude mitochondrial fraction of rat brain was homogenized with distilled water and centrifuged, most of guanylate cyclase activity was detected in the soluble fraction. The total guanylate cyclase activity recovered in the soluble fraction was 5- to 8-fold higher than that of the crude mitochondrial fraction. The greater recovery of guanylate cyclase activity was found to be due to a release of an endogenous activating factor for guanylate cyclase. The activating factor was partially purified by acid extraction followed by a gel filtration and ion exchange resin columns. The factor was a dialyzable small molecule. The molecular weight was estimated to be between 300 and 600 by a Sephadex G-15 column and Diaflo ultrafilter membranes. It was stable in dilute acids, but labile in alkaline solution. It was readily soluble in water, but insoluble in organic solvents. Treatment with various enzymes, so far as tested, failed to abolish the activity. The activating factor stimulated the initial velocity of the reaction. It altered neither the Km value for GTP nor the dependency of the enzyme on divalent metals. The activation by the factor was due to an increase in the Vmax of the reaction. The activation was prevented by lysolecithin, Lubrol PX, hydroxylamine, methylhydroxylamine, or hemoglobin.
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PMID:Endogenous activating factor for guanylate cyclase in synaptosomal-soluble fraction of rat brain. 2 Nov 82

Guanylate cyclase from the rat renal medulla is found in both the soluble and particulate fractions of the cell. Sucrose density gradient centrifugation and gel filtration in H2O and D2O indicate that the enzyme from the soluble cell fraction has the following properties: S20w, 6.3 S; Stokes radius, 54 A; partial specific volume, 0.75 ml/g; mass, 154,000 daltons; f/fo, 1.4; axial ratio (prolate ellipsoid), 7. The addition of 0.1% Lubrol PX to this fraction activates the enzyme and changes thartial specific volume, 0.74 ml/g; mass, 148,000 daltons; f/fo, 1.6; axial ratio (prolate ellipsoid), 11. These findings show that detergent activates the enzyme by changing its conformation and not simply by dispersing nonsedimentable membrane fragments. The dimensions of this guanylate cyclase in detergent are very similar to those of detergent-solubilized adenylate cyclase from the same tissue (Neer, E.J. (1974) J. Biol. Chem. 249, 6527-6531). Guanylate cyclase can be solubilized from the particulate cell fraction with 1% Lubrol PX but has properties quite different from those of the guanylate cyclase in the soluble cell fraction. It is a large aggregate with a value of S20,w of about 10 S, Stokes radius of 65 A, and a mass of approximately 300,000 daltons. However, the peaks of guanylate cyclase activity in column effluents and sucrose density gradients are very broad indicating a mixture of different size proteins. The conditions used to solubilize guanylate cyclase from the particulate fraction also solubilize adenylate cyclase, and the two activities can be separated on the same sucrose gradient. Studies of this sort require a rapid, accurate guanylate cyclase assay. We have developed an assay for guanylate cyclase activity which meets these criteria by adapting the competitive protein binding assay for guanosine cyclic 3':5' monophosphate originally described by Murad et al. (Murad, F., Manganiello, V., and Vaughn, M. (1971) Proc. Natl. Acad. Sci. U.S.A. 68, 736-739).
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PMID:Guanylate cyclase from the rat renal medulla. Physical properties and comparison with adenylate cyclase. 24 Aug 41

Current information on the intestinal secretory mechanism and on the actions of the enterotoxins from Vibrio cholerae and Escherichia coli are reviewed. These enterotoxins, through their effects on the metabolism of cyclic nucleotides, both inhibit active absorption and stimulate active secretion of water and electrolytes in the small intestine. the enterotoxin of V. chol erae and the heat-labile enterotoxin of E. coli affect these activities by stimulating adenylate cyclase, and the heat-stable enterotoxin of E. coli does so by stimulating guanylate cyclase.
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PMID:Modes of action of enterotoxins from Vibrio cholerae and EScherichia coli. 39 84

The size distribution of adenylate cyclase from the rat renal medulla solubilized with the nonionic detergents Triton X-100 and Lubrol PX was determined by gel filtration and by centrifugation in sucrose density gradients made up in H2O or D2O. The physical parameters of the predominant form in Triton X-100 are s20,w, 5.9S; Strokes radius, 62 A; partial specific volume (v), 0.74 ml/g; mass, 159,000 daltons; f/f0, 1.6; axial ratio (prolate ellipsoid), 11. For the minor form the values are: s20w, 3.0; Stokes radius, 28 A; mass, 38,000 daltons; f/f0, 1.2. The corresponding values determined in Lubrol PX are similar. The value for V for the enzyme indicates that it binds less than 0.2 mg detergent/mg protein. Since interactions with detergents probably substitute for interactions with lipids and hydrophobic amino acid side chains, these findings suggest that no more than 5% of the surface of adenylate cyclase is involved in hydrophobic interactions with other membrane components. Thus, most of the mass of the enzyme is not deeply embedded in the lipid bilayer of the plasma membrane. Similar studies have been performed on the soluble guanylate cyclase of the rat renal medulla. In the absence of detergent, the molecular properties of this enzyme are: s20w, 6.3S; Stokes radius, 54 A, V, 0.75 ml/g; mass, 154,000 daltons f/f0, 1.4; Axial ratio, 7. The addition of 0.1% Lubrol PX to this soluble enzyme increases it activity two- to fourfold and changes the physical properties to: s20,w, 5.5S; Stokes radius, 62 A; V, 0.74 ml/g; mass, 148,000 daltons, f/f0, 1.6; axial ratio, 11. These results show that Lubrol PX activates the enzyme by causing a conformational change with unfolding on the polypeptide chain. Guanylate cyclase from the particulate cell fraction can be solubilized with Lubrol PX but has properties quite different from those of the enzyme in the soluble cell fraction. It is a heterogeneous aggregate with s20,w, 10S; Stokes radius, 65 A; mass about 300,000 daltons. The conditions which solubilize guanylate cyclase also solubilize adenylate cyclase and the two activities can be separated on the same sucrose gradient.
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PMID:The size of adenylate cyclase and guanylate cyclase from the rat renal medulla. 125 62

Studies with Escherichia coli-induced heat-stable enterotoxin (STa), an activator of intestinal particulate guanylate cyclase, have established an independent role for cyclic guanosine monophosphate (cGMP) as an intracellular mediator of intestinal salt and water secretion. The present study addressed whether atriopeptins (APs), known activators of particulate guanylate cyclase in other tissues, function as physiological agonists for cGMP-linked Cl- secretion in intestine. APs, in contrast to STa, caused no or only minor changes in cGMP levels in freshly isolated rat intestinal villus and crypt cells and in cultured human colon carcinoma cell lines (HT29glc-, CaCo-2, and T84). Conversely, APs, but not STa, induced a large increase in intracellular cGMP levels in the undifferentiated small intestinal cell lines IEC-6, IEC-18, and INT407. Addition of AP II (atrial natriuretic peptide fragment 5-27) to stripped mucosa of rat proximal colon in Ussing chambers caused a transient increase in the transepithelial potential difference (PD), which most likely represents an increase in Cl- secretion. In contrast, a sustained increase in PD was observed in response to STa or 8Br-cGMP. The AP II-provoked increase in PD was blocked by the neurotoxin tetrodotoxin. Immunohistochemical detection of cGMP in this tissue provided evidence for a different localization pattern of cells responding with an increase in cGMP levels to STa (colonocytes and goblet cells) or AP (specific cells in the submucosa) in rat proximal colon. This indicates that APs, unlike STa, do not directly stimulate the colonic epithelial cells but possibly provoke Cl- secretion by release of a neurotransmitter in the submucosa.
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PMID:Atriopeptins and Escherichia coli enterotoxin STa have different sites of action in mammalian intestine. 131 72

Studies were performed to examine the regulation of atrial natriuretic peptide- (ANP) stimulated guanylate cyclase in the the inner medulla. Primary cultures of rat inner medullary collecting tubular cells exposed to 10(-7) M ANP increased cGMP formation to 31.2 +/- 1.8 compared to the basal production of 2.1 +/- 0.6 fm/micrograms protein. This response did not appear to be transduced via a Gi protein, as preincubation with pertussis toxin did not alter the response to 10(-7) M ANP, and saponized cells exposed to 10 microM GTP gamma S did not enhance the response to ANP (77.3 +/- 5.9 vs. 86.7 +/- 6.3 g/micrograms). Likewise, changes in extracellular Ca2+ from 0.5 to 3.0 mM, decrements in intracellular Ca2+ with EGTA or increments in intracellular Ca2+ with ionomycin (5 microM) did not significantly alter the response to ANP. Neither activation of protein kinase A with forskolin (36.5 +/- 5.1) nor of protein kinase C with s,n-1,2-dioctanoylglycerol (33.2 +/- 2.5) altered the response to 10(-7) M ANP (32.2 +/- 3.3, NS). As the inner medullary environment was hypertonic, the effect of altering tonicity was studied. Cells grown for 48 hours in hypertonic media (600 mOsm/kg H2O) displayed enhanced response to 10(-8) and 10(-7) M ANP when osmolality was raised by either Na+ alone or in combination with urea, but not by urea alone. Our studies demonstrate that ANP-stimulated guanylate cyclase is insensitive to alterations in either intra- or extracellular Ca2+, is not subject to inhibition by protein kinase, and does not involve a pertussis-sensitive G protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of atrial natriuretic peptide-stimulated cGMP production in the inner medulla. 131 78

Atrial natriuretic peptide (ANP) has been shown to affect water and ion transport and specific ANP binding has been identified in several secretory tissues. ANP commonly acts via stimulation of membrane-bound particulate guanylate cyclase with the production of cyclic guanosine monophosphate (cGMP). We questioned whether ANP played a role in the complex cyclic transformation of the endometrium into a secretory tissue, and whether its action was cGMP mediated. Endometrium was obtained by biopsy in regularly menstruating women and stromal cells were isolated and cultured for use in this study. ANP competitive binding assays were performed using 125I-labeled ANP (0.1 nmol/L) and increasing concentrations of unlabeled ANP (0-1000 nmol/L). Optimal binding was obtained after 3-h incubation at 4 C and binding characteristics, including dissociation constant and binding site quantity, were estimated by Scatchard analysis. Specific, high affinity (dissociation constant, 0.078 +/- 0.004 nmol/L) and low capacity (4,877 +/- 1,951 binding sites/cell) ANP binding was identified, with nonspecific binding representing less than or equal to 16% of total binding. Evaluation of ANP-stimulated cyclic nucleotide production revealed an increase in cGMP production, with a 7-fold increase at 1000 nmol/L ANP, and no effect on cAMP production. In conclusion, we have identified specific high affinity receptors for ANP in human endometrial cells, suggesting a role for ANP in endometrial cell function and/or development mediated via cGMP production. We propose that ANP may affect local salt and water metabolism, may be involved in the secretory evolution of glandular and stromal cells, and may further facilitate endometrial development via modulation of local vascular tone and endothelial permeability.
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PMID:Atrial natriuretic peptide receptors in human endometrial stromal cells. 132 28

The distribution of binding sites for atrial natriuretic peptide (ANP) has been examined in frozen sections of the guinea pig inner ear by means of autoradiography. The highest density was found in the stria vascularis of all cochlear turns. In membrane preparations of stria vascularis in vitro, the production of the second messenger cGMP was strongly stimulated by synthetic ANP in a dose dependent manner. Adenylate cyclase was neither stimulated nor inhibited by ANP, thus suggesting, that the binding sites coincide with an ANP receptor, which is coupled to guanylate cyclase but not negatively coupled to an adenylate cyclase molecule. The production of cyclic GMP could not be reduced by GDP-beta S, a strong inhibitor of the Gs protein. We conclude the existence of an ANP receptor-guanylate cyclase signal transfer system, similar to the beta 2 receptor-adenylate cyclase system in the inner ear, without coupling to a G protein. ANP might play a role in sodium and water regulation of the endolymph and might antagonize the action of vasopressin.
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PMID:Binding sites of atrial natriuretic peptide (ANP) in the mammalian cochlea and stimulation of cyclic GMP synthesis. 133 79


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