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)

To determine whether endothelium-derived relaxing factor (EDRF) contributes to the regulation of endothelial permeability, the transendothelial flux of 14C-sucrose, a marker for the paracellular pathway across endothelial monolayers (Oliver, J. Cell. Physiol. 145:536-548, 1990), was examined in monolayers of bovine aortic endothelial cells grown on collagen-coated filters. The permeability coefficient of 14C-sucrose was significantly decreased by 10(-3) M 8-Bromoguanosine 3',5'-cyclic monophosphate or by 5 x 10(-6) M glyceryl trinitrate, an activator of soluble guanylate cyclase. Depletion of L-arginine from endothelial monolayers increased 14C-sucrose permeability from 3.21 +/- 0.59 to 3.88 +/- 0.50 x 10(-5) cm.sec-1 (mean +/- SEM; n = 6; P < 0.05). The acute administration of 5 x 10(-4) M L-arginine to monolayers depleted of this amino acid decreased 14C-sucrose permeability from 2.91 +/- 0.27 to 2.52 +/- 0.26 x 10(-5) cm.sec-1 (n = 11; P < 0.05). 14C-sucrose permeability was increased by 10(-7) M bradykinin and this effect was enhanced by the presence of each one of the following compounds: 10(-5) M methylene blue, 4 x 10(-6) M oxyhemoglobin, 5 x 10(-4) M NG-methyl-L-arginine or 5 x 10(-4) M N omega-nitro-L-arginine. These results suggest that EDRF contributes to the sealing of the endothelial monolayer and that EDRF released by bradykinin acts as a feedback inhibitor attenuating the increase in endothelial permeability induced by this peptide. Because endothelial cells have the ability to contract and relax and possess guanylate cyclase responsive to nitric oxide, our results suggest that EDRF decreases 14C-sucrose permeability by relaxing endothelial cells, thereby narrowing the width of endothelial junctions.
 ...
PMID:Endothelium-derived relaxing factor contributes to the regulation of endothelial permeability. 136 53

Recently we demonstrated that the vascular response to angiotensin II (A-II) was attenuated in an endothelium-dependent manner by using the isolated ring specimen iliac arteries of pregnant rabbits. In this paper we investigated the possibility that three vasoactive substances, thromboxane A2(TXA2), prostacyclin (PGI2), and endothelium-derived nitric oxide (EDNO), might be involved in this refractoriness to A-II during pregnancy, by measuring the changes in the vascular response to A-II (pA2, intrinsic activity) of the isolated arterial rings of rabbits before and after the addition of an inhibitor specific for each of these three substances. Sodium ozagrel, TXA2 synthetase inhibitor, decreased the vascular response to A-II more in the blood vessels of pregnant rabbits, regardless of whether the endothelium was intact or denuded, than in the blood vessels of non pregnant rabbits. Tranylcypromine, a PGI2 synthetase inhibitor, significantly increased contractility in the blood vessels with intact endothelium of pregnant rabbits (i.a. = 1.39 +/- 0.099, n = 11, mean +/- SEM), compared to that in the blood vessels with intact endothelium of non pregnant rabbits (i.a. = 1.08 +/- 0.090, n = 7). Methylene blue, a guanylate cyclase inhibitor which blocks the effect of EDNO, amplified the vascular response in blood vessels with intact endothelium of both groups, and more intensely in the blood vessels of pregnant rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Effect of endothelium-derived nitric oxide and prostaglandins on the endothelium-dependent vascular refractoriness to angiotensin II in pregnant rabbits]. 145 44

The proposed actions of atrial natriuretic factor (ANF) are mediated through specific plasma membrane (R1) receptors coupled to guanylate cyclase. A second receptor, R2, has been characterized by its ability to bind to an acyclic, truncated ANF analog (C-ANF4-23). The ANF-R2 receptor has not been identified in the fetus. Our study was conducted to determine the effects of C-ANF on fetal renal and cardiovascular function and plasma ANF clearance rates. Chronically catheterized ovine fetuses (n = 6) at 111 to 117 d gestation (term 145 d) received a C-ANF infusion (1 microgram/min/kg) for 30 min followed by a combined infusion of C-ANF and ANF (C-ANF, 1 microgram/min/kg; ANF, 100 ng/min/kg) for an additional 30 min. C-ANF infusion significantly increased (mean +/- SEM) plasma ANF concentration (437 +/- 45 to 1067 +/- 297 pg/mL), urinary flow rate (0.26 +/- 0.04 to 0.38 +/- 0.07 mL/min/kg), sodium excretion (12.9 +/- 3.5 to 21.7 +/- 6.1 mumol/min/kg), and osmolar clearance (0.14 +/- 0.02 to 0.21 +/- 0.04 mL/min/kg) (p less than 0.05). The combined C-ANF/ANF infusion further increased plasma ANF concentration to 2394 +/- 532 pg/mL and resulted in significant increases in urinary flow rate, sodium excretion, osmolar clearance, GFR, and free water clearance compared with C-ANF infusion alone (p less than 0.05). These renal responses, however, were not significantly different from the responses to ANF infusion alone (100 ng/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of a ring-deleted atrial natriuretic factor analogue on ovine fetal renal and cardiovascular function. 164 30

Atrial natriuretic factor (ANF) has been identified in fetal and newborn mammals, and considerable data regarding fetal ANF metabolism are available. However, there is limited information concerning ANF receptors or receptor ontogenesis in developing mammals. We measured ANF receptor binding capacity, affinity, and ANF-induced cyclic GMP (cGMP) generation in isolated renal glomeruli from fetal (29 d gestation, term = 31 d), newborn (3 d), juvenile (28 d), and adult rabbits. The (mean +/- SEM) glomerular receptor binding capacity values for ANF in fetal and newborn animals (10 +/- 1 and 12 +/- 3 fmol/mg protein) were similar and significantly lower than the values for juvenile and adult animals (30 +/- 8 and 74 +/- 15 fmol/mg protein, respectively). In contrast, there were no significant differences in ANF receptor affinity values or dose-dependent increases in ANF-stimulated cGMP generation among the age groups studied. In competition studies, we observed effective displacement of 125I-ANF by C-ANF4-23, a ring-deleted ANF analogue, in adult, juvenile, and newborn glomeruli; however, C-ANF displaced only about 50% of the 125I-ANF in fetal tissue. The addition of C-ANF did not elicit cGMP generation, nor did C-ANF affect ANF-induced cGMP generation in fetal, newborn, or adult glomeruli. These results indicate that 1) the ANF receptor-guanylate cyclase system is intact in 29-d fetal rabbit glomeruli, and 2) the ANF-induced cGMP formation is similar in fetal and adult animals, whereas receptor binding capacity is relatively higher in adult glomeruli. These results suggest a higher proportion of nonguanylate cyclase-coupled ANF receptors in the mature rabbit.
 ...
PMID:Ontogeny of atrial natriuretic factor receptors and cyclic GMP response in rabbit renal glomeruli. 165 34

Female sex pheromones applied to freshly isolated, living antennae of male Antheraea polyphemus and Bombyx mori led to an increase of cGMP. A 1:1 mixture of 2 pheromone components of Antheraea polyphemus blown for 10 sec in physiological concentrations over their antennal branches raised cGMP levels about 1.34-fold (+/- 0.08 SEM, n = 23) from a basal level of 3.0 +/- 0.6 (SEM, n = 20) pmol/mg protein. Similarly, bombykol elicited a 1.29-fold (+/- 0.13 SEM, n = 23) cGMP increase in antennae of male Bombyx mori from a basal level of 2.7 +/- 0.5 (SEM, n = 24) pmol/mg protein. No cross-sensitivity was found with respect to pheromones from either species. In antennae of female silkmoths, the cGMP response was missing upon stimulation with their own respective pheromones according to the known lack of pheromone receptor cells in the female. cAMP levels in the male antennae of 14.2 +/- 2.9 (SEM, n = 4) pmol/mg protein in A. polyphemus and 15.0 +/- 3.0 (SEM, n = 5) pmol/mg protein in B. mori were not affected by pheromone stimulation. Within 1-60 sec, the extent of cGMP increase in B. mori was independent of the duration of pheromone exposure. The levels of cGMP in pheromone-stimulated antennae of both species remained elevated for at least 10 min, i.e., much longer than the duration of the receptor potential measured in single-cell recordings. Guanylate cyclase activity was identified in homogenates of male and female antennae from both species. The Km of the guanylate cyclase from male B. mori for the preferential substrate MnGTP was 175 microM.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cyclic GMP levels and guanylate cyclase activity in pheromone-sensitive antennae of the silkmoths Antheraea polyphemus and Bombyx mori. 197 Mar 56

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.
 ...
PMID:Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line. 256 5

Experiments were designed to investigate whether platelet activation is modulated by endothelium-derived relaxant factor (EDRF) which has been shown to induce vascular smooth muscle relaxation by direct stimulation of soluble guanylate cyclase. EDRF was released from cultured bovine endothelial cells, grown on microcarrier beads, by stimulation with thimerosal in the presence of indomethacin. EDRF had no effect on the intracellular free calcium concentration (Cai2+, measured with the fluorescent indicator indo-1) of resting washed human platelets but significantly attenuated the thrombin-induced rise of Cai2+ from 896 +/- 99 (SEM) to 509 +/- 48 nmol/l. EDRF significantly increased platelet cyclic GMP levels from 0.25 +/- 0.04 to 2.5 +/- 0.4 pmol/10(8) platelets and reduced the thrombin-induced aggregation to 23 +/- 3% of control. EDRF had no effect on Cai2+, cyclic GMP or aggregation after a 3 min storage interval, but superoxide dismutase (shown to increase stability of the labile factor) significantly augmented the EDRF effects on Cai2+. The antiaggregatory potency of EDRF was completely abolished in the presence of hemoglobin. The results characterize EDRF as a potent cyclic GMP-dependent antiaggregatory factor which may act synergistically in vivo with the cyclic AMP-dependent inhibitory effect of prostacyclin.
 ...
PMID:Endothelium-derived relaxant factor inhibits platelet activation. 283 May 46

The vasodilating potency of alpha-human atrial natriuretic peptide (alpha-hANP) was investigated in the forearms of 16 normotensive subjects, 22 to 48 (mean 28) years old, with the use of venous occlusion plethysmography. alpha-hANP, 0.005 to 1.5 micrograms/min/100 ml forearm volume (FAV), infused in nine dose steps into the brachial artery increased forearm blood flow (FAF; ml/min/100 ml FAV) from 2.8 +/- 0.4 (SEM) to a maximum of 9.6 +/- 1.1. Forearm vascular resistance (mean arterial pressure/FAF) decreased by 72%. The alpha-hANP dose that produced a 50% vasodilator response was 0.093 +/- 0.016 microgram/min/100 ml FAV (n = 11) and it resulted in a venous plasma concentration of ANP (pANP) of 115 +/- 7 pmol/liter (normal 2 to 80; radioreceptor assay). Intraindividually, the maximum dose of alpha-hANP induced an increase in FAF that was 60% of the maximum response to sodium nitroprusside (14.1 +/- 1.8). Combined infusions (n = 9) of maximum forearm vasodilator doses of alpha-hANP and nitroprusside increased FAF to 22.7 +/- 3.4; this additive vasodilator effect of alpha-hANP and nitroprusside is consistent with their different actions on the guanylate cyclase system. In man, the direct vasorelaxant effect of alpha-hANP occurs at concentrations within the upper normal range of pANP, suggesting a physiologic vasodilator role for alpha-hANP.
 ...
PMID:The vasodilator potency of atrial natriuretic peptide in man. 294 42

Plasma concentrations of cardiodilatin, the peptide sequence at the amino terminal of the pro-atrial natriuretic peptide, in 17 normal subjects ranged from 59 to 202 (mean 118 (SEM) (9] pmol/l. Recumbency increased the mean (SEM) concentration to 160 (13) pmol/l. The plasma concentration of cardiodilatin in 24 patients with congestive cardiac failure was much higher (964 (175) pmol/l) than in the normal subjects. It was highest in those with heart failure in New York Heart Association functional classes III and IV and the concentration correlated both with atrial natriuretic peptide concentrations and left ventricular ejection fraction. Concentrations rose during induced tachycardia in three patients tested. Chromatography showed a single clean peak of plasma cardiodilatin immunoreactivity. It seems that cardiodilatin is a second circulating cardiac peptide that is jointly released with atrial natriuretic peptide by common stimuli. Other workers have reported that, like atrial natriuretic peptide, three partial cardiodilatin sequences can stimulate renal particulate guanylate cyclase and increase cyclic guanosine monophosphate. The simultaneous release of cardiodilatin in higher circulating concentrations than atrial natriuretic peptide may be relevant to the finding that appropriate concentrations of exogenous atrial natiuretic peptide alone do not produce the full renal effects associated with endogenous peptide release.
 ...
PMID:Increase in plasma concentrations of cardiodilatin (amino terminal pro-atrial natriuretic peptide) in cardiac failure and during recumbency. 297 Feb 69

Murine neuroblastoma cells (clone N1E-115) possess both high- and low-affinity muscarinic receptors. The low-affinity muscarinic receptor, when stimulated, initiates the formation of cyclic GMP by activating the enzyme guanylate cyclase; whereas stimulation of the high-affinity receptor inhibits prostaglanding E1-mediated cyclic AMP formation by inhibiting the enzyme adenylate cyclase. We have reported that lithium ion (Li+) inhibits cyclic GMP formation mediated by the muscarinic receptor agonist, carbachol, in a concentration-dependent manner and that neither ammonium nor sodium ions have such an effect. We extended this study to show that Li+ was an apparently noncompetitive inhibitor of the low-affinity muscarinic receptor with an IC50(+/- SEM) = 13.6 +/- 0.8 mM. In addition, Li+ with a similar IC50 inhibited the cyclic GMP response in intact cells to sodium azide, which is thought to stimulate guanylate cyclase directly. Moreover, though Li+ was found to have a slight inhibitory effect on prostaglandin E1-stimulated cyclic AMP formation (15% inhibition at 10 mM), it had no effect on the function of the high-affinity muscarinic receptor in intact murine neuroblastoma cells.
 ...
PMID:Lithium ions inhibit function of low- but not high-affinity muscarinic receptors of murine neuroblastoma cells (clone N1E-115). 299 50


1 2 3 Next >>