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)

Centrifugation of homogenates of bovine retinas to isopycnic equilibrium in sucrose density gradients yielded three partially overlapping bands of particles which were, in the order of increasing density: (a) photoreceptor cell (rod) outer segments; (b) plasma membranes, lysosomes, and large fragments of endoplasmic reticulum; and (c) mitochondria. The only enzyme activity investigated which had a peak coinciding only with outer segment fractions was guanylate cyclase. Enzyme activities with peaks in both the outer segment and denser fractions included 5'-nucleotidase and cyclic GMP phosphodiesterase. Enzyme activities with peaks only in the denser fractions included sodium and potassium ion-activated ATPase ((Na+ + K+)-ATPase), adenylate cyclase, cyclic AMP phosphodiesterase, beta-glucosidase, beta-galactosidase, and succinate-dependent cytochrome c reductase. These results suggest that some of the activities once thought to be present in rod outer segments are actually present in particles from elsewhere in the retina which contaminate rod outer segment preparations.
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PMID:Distribution of enzyme activities in subcellular fractions of bovine retina. 0 65

Obstetric hemorrhage may occur throughout pregnancy and the puerperium. The purpose of this study was to investigate the reactivity of isolated, suffused uterine arteries from obstetric patients with uncontrollable uterine bleeding and to compare those blood vessels with uterine arteries from patients undergoing cesarean hysterectomy for other medical reasons (control patients). The uterine arteries from the control patients (n = 9) responded with maximal or near-maximal constriction to norepinephrine (30 mumol/L, 3.6 +/- 1 gm), potassium chloride (75 mmol/L, 10.2 +/- 3 gm), prostaglandin F2 alpha (30 mumol/L, 1.8 +/- 1 gm), and arginine vasopressin (1 mumol/L, 18.8 +/- 2.6 gm). In uterine arteries from five patients with uncontrollable bleeding, the constrictor responses to the same drugs were markedly depressed: norepinephrine (30 mumol/L, 0.5 +/- 0.2 gm), potassium chloride (75 mmol/L, 1.9 +/- 0.8 gm); prostaglandin F2 alpha (30 mumol/L, 0 gm), and arginine vasopressin (1 mumol/L, 0.2 +/- 0.05 gm). Uterine arteries from two patients exhibited no constrictor responses to norepinephrine (30 mumol/L), potassium chloride (75 mmol/L), prostaglandin F2 alpha (30 mumol/L), or arginine vasopressin (1 mumol/L). The impaired responses to the vasoconstrictor drugs were not reversed by indomethacin (1 mumol/L), which is an inhibitor of prostaglandin synthetase; methylene blue (10 mumol/L), which is a blocker of endothelium-derived relaxing factor activation of guanylate cyclase; or propranolol (1 mumol/L), a beta-adrenergic receptor antagonist. The levels of adenosine 3':5'-cyclic monophosphate were not elevated in the uterine arteries from the patients with obstetric hemorrhage. The impaired reactivity to the multiple vasoconstrictors implies that a mechanism involved in constriction common to all of the constrictors is depressed or blocked. Furthermore, the depression or lack of reactivity of these isolated uterine arteries is not mediated by vasodilatory prostaglandins, endothelium-derived relaxing factor, beta-adrenergic receptors, or elevated levels of adenosine 3':5'-cyclic monophosphate. The results suggest that obstetric hemorrhage involves, in part, a lack of constrictor reactivity of the uterine vasculature.
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PMID:Lack of reactivity of uterine arteries from patients with obstetric hemorrhage. 131 76

A possible mechanism of the vasodilator effect of scoparone was investigated. Scoparone (10(-6)-3 x 10(-5) M) dilated rat aortic rings precontracted with phenylephrine in a dose-dependent manner. The presence of endothelium facilitated the vasodilator effect. Scoparone depressed the contractile responses to phenylephrine and serotonin, but not that to potassium chloride. Both the vasoconstriction and O2- production induced by alloxan, a diabetogenic compound, were depressed by scoparone. It appears that scoparone exhibited a free radical scavenger-like effect. The dilatation elicited by acetylcholine was potentiated by scoparone. The dilator activity of scoparone was markedly inhibited by methylene blue and hemoglobin, guanylate cyclase inhibitors. Furthermore, the basal guanosine 3',5'-cyclic monophosphate (cGMP) level was elevated in the presence of scoparone. The dilator activity of scoparone was also inhibited by quinacrine (inhibitor of phospholipase A2) and indomethacin (inhibitor of cyclooxygenase). Our results showed further that the output of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin, was enhanced by scoparone. It is suggested that the vasodilator effect of scoparone in rat aorta may be mediated through the enhancement of prostacyclin release, protecting against EDRF inactivation, and activating guanylate cyclase.
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PMID:Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. 132 21

The 98 amino acid (a.a.) N-terminus of the 126 a.a. atrial natriuretic factor (ANF) prohormone contains three peptides consisting of a.a. 1-30 (proANF 1-30), a.a. 31-67 (proANF 31-67) and a.a. 79-98 (proANF 79-98) with blood pressure lowering, sodium and/or potassium excreting properties similar to atrial natriuretic factor (a.a. 99-126, C-terminus of prohormone). ProANF 1-30 and proANF 31-67 have separate and distinct receptors from ANF in both vasculature and in the kidney to help mediate the above effects. At the cellular level proANFs 1-30, 31-67, and 79-98 as well as ANF's effects are mediated by enhancement of the guanylate cyclase (EC 4.6.1.2)-cyclic GMP system in vasculature and in the kidney. These peptides from the N-terminus of the ANF prohormone circulate normally in man and in all animal species tested. The object of the present investigation was to determine if these peptides have the ability to enhance either guanylate cyclase and/or adenylate cyclase in a variety of other tissues in addition to kidney and vasculature. ProANF 1-30, proANF 31-67, proANF 79-98, and ANF all increased rat lung, liver, heart and testes, but not spleen, particulate guanylate cyclase 2- to 3-fold at their 100 nM concentrations. Dose response curves revealed that maximal stimulation of particulate guanylate cyclase activity by these newly discovered peptides was at their 1 microM concentrations, with no further increase in activity above their 1 microM concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peptides from the N-terminus of the atrial natriuretic factor prohormone enhance guanylate cyclase activity and increase cyclic GMP levels in a wide variety of tissues. 135 37

1. Nicorandil, pinacidil and lemakalim relaxed precontracted rings of canine cerebral artery. 2. The order of potency was lemakalim greater than nicorandil approximately equal to pinacidil, but all these agents were less effective than nimodipine. 3. The effects of nicorandil were inhibited by methylene blue but not by glibenclamide, while the effects of pinacidil and lemakalim were inhibited by glibenclamide but not by methylene blue. 4. Thus nicorandil probably causes relaxation mostly by effects on guanylate cyclase while lemakalim and pinacidil produce the same effect by action at ATP-dependent potassium channels.
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PMID:Vasodilatation of canine cerebral arteries by nicorandil, pinacidil and lemakalim. 135 69

The nearly total inhibition of development of pharmacological tolerance to an organic nitrate is reported here for the first time. The development of in vitro tolerance in the rabbit aorta to isosorbide-5-mononitrate (CAS 87-33-2) was potently inhibited by five structurally unrelated antioxidants--diaminodurol, ascorbic acid, potassium sulphite, pyrogallol and quercetin. Diaminodurol, ascorbic acid and potassium sulphite decreased, but quercetin increased, the spasmolytic activity of isosorbide-5-mononitrate. Diaminodurol, potassium sulphite, quercetin and ascorbic acid potently inhibited the spasmolytic activity of nitric oxide (NO). Quercetin also inhibited the development of in vitro tolerance to glyceryl trinitrate. It is suggested that tolerance to organic nitrates is the result of biochemical damage caused by a reactive intermediate such as NO. To test this possibility directly the effect of pretreatment with NO on the spasmolytic activity of glyceryl trinitrate (CAS 55-63-0) was examined. This pretreatment produced a small but significant tolerance to glyceryl trinitrate and to SIN-1 (3-morpholinosydnone imine), which also acts through guanylate cyclase. There was no effect on the activity of the unrelated vasodilators nitrendipine and theophylline. It is concluded that the reaction between NO and soluble quanylate cyclase is a real but minor cause of tolerance to organic nitrates. Other possible mechanisms of tolerance development are discussed.
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PMID:Total prevention of the development of in vitro tolerance to organic nitrates. Experiments with antioxidants. 135 61

Atrial natriuretic peptide (ANP) inhibits aldosterone secretion evoked by its physiological secretagogues by a mechanism(s) likely to involve intracellular messengers. When one examines the results of various investigations so far, this premise, although not definitive yet, seems to be supported. Therefore a brief perspective on the cellular messengers of the various secretagogues is provided before the inquiry into the possible mechanism of action of ANP. The receptors of ANP in the adrenal cells have been identified and characterized. ANP inhibits adenylate cyclase in various tissues through an inhibitory G protein, which appears to explain in part the inhibitory effect of ANP on adrenocorticotropin-induced aldosterone secretion. However, there could be other possible effects of ANP as discussed. ANP probably inhibits aldosterone secretion evoked by angiotensin II and potassium by interfering with the appropriate changes in calcium flux and cell calcium concentration, concomitants of stimulation by these secretagogues. The potential modes of these effects are probed. The role of guanosine 3',5'-cyclic monophosphate, which is increased by receptor activation of guanylate cyclase by ANP and is thought to play a major role in the biological effects of ANP in some other tissues, remains controversial in the aldosterone-lowering effect of ANP, and this is also discussed extensively in this review.
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PMID:Atrial natriuretic peptide-induced inhibition of aldosterone secretion: a quest for mediator(s) 135 32

1. Solitary horizontal cells were isolated from catfish retinas and their membrane current was recorded with a whole-cell voltage clamp. Reducing the extracellular Ca2+ concentration produced a current that could be suppressed by dopamine. This Ca(2+)- and dopamine-sensitive current is hereafter termed I gamma. The voltage dependence, cytoplasmic regulation, and permeability of the I gamma channel suggest that it is half of a gap-junction channel. 2. I gamma was voltage and time dependent. In the steady state, the current-voltage relation displayed outward rectification at voltages more depolarized than 0 mV and a negative resistance region at voltages more hyperpolarized than -15 mV. The reversal potential was 3.3 +/- 1.5 mV when NaCl was the predominant extracellular salt and potassium-D-aspartate was the predominant intracellular salt. 3. The size of I gamma depended on the extracellular Ca2+ concentration. I gamma was maximal at external Ca2+ concentrations below 10 microM, half-maximal at 220 microM-Ca2+, and reduced to less than 4% of its maximum amplitude at external Ca2+ concentrations above 1 mM. Increasing the extracellular Ca2+ concentration reduced the amplitude of I gamma without changing the shape of the current-voltage relation or the kinetics of inactivation. Thus, rectification does not result from a voltage-dependent block by extracellular Ca2+. 4. Patches of cell membrane were voltage clamped in both the cell-attached and excised-patch configurations. In the cell-attached configuration, the addition of dopamine to the solution outside the patch pipette blocked the opening of channels within the membrane patch. Thus, dopamine closes I gamma channels by initiating an intracellular messenger cascade. In the excised-patch configuration, a maximum conductance of 145 pS was measured while Cs+ and tetraethylammonium+ (TEA+) were the only monovalent cations on both sides of the membrane. 5. The ability of dopamine to suppress I gamma was blocked by introducing an inhibitor of the cyclic AMP-dependent protein kinase, PKI5-24, into the cytoplasm. Thus, the action of dopamine is mediated by a pathway that includes the activation of a cyclic AMP-dependent kinase. 6. I gamma was suppressed by nitroprusside, an agent which activates guanylate cyclase and increases the intracellular cyclic GMP concentration. The effect of nitroprusside was not altered by the intracellular application of PKI5-24. Thus, nitroprusside suppresses I gamma through a pathway that does not include the activation of a cyclic AMP-dependent kinase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hemi-gap-junction channels in solitary horizontal cells of the catfish retina. 138 84

The cell membrane of vascular smooth muscle is lined with many receptor sensitive to signals emitted by the vessel wall or transported in the blood stream. Recent data on the mechanisms by which these receptors regulate vascular tone enable them to be classified into two main groups. The first group includes the receptors carried by the membrane proteins which are under their direct control; ATP-P2x receptors on Na+ and Ca2+ channels, pharmacological receptors (dihydropyridines, diltiazem, phenylalkylamines) situated on a voltage operated channel, receptors to cromakaline-like substances associated with a potassium channel, receptors to atriopeptines (ANF-B) with guanylate cyclase activity. The second group of receptors act through the intermediary of the G protein (which has a high affinity for guanylic nucleotides); it regulates the activity of an effector which may be an enzyme or an ionic channel. The receptors of this type which have been identified in vascular smooth muscle are: --positively (beta-adrenergic, DA1-dopaminergic, P1 purinergic or H2-histaminic) or negatively coupled (alpha 2-adrenergic) to adrenylate cyclase; --positively coupled to C phospholipase (angiotensin II, vasopressin V1, 5-H-T2, alpha 1-adrenergic, M1-cholinergic, H1-histaminic). In addition, the same receptor may act by different mechanisms (V1-vasopressin, alpha 2-adrenergic, for example). Whatever the initial mechanism of action, all these receptors influence the contraction by changing ionic permeability or by producing secondary relaxing (cyclic AMP, cyclic GMP) or contractility messengers (inositol phosphates, diacylglycerol).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Current data of the membrane receptors of the vascular smooth muscle fibers]. 164 53

The possible mechanism underlying the vasorelaxant effect of emodin isolated from a Chinese herb, was investigated in this study. Emodin dose dependently relaxed isolated vascular rings of human internal mammary artery and saphenous vein, rabbit thoracic aorta, abdominal aorta and mesenteric artery, and rat thoracic aorta. There were no differences in the sensitivity (IC50) and maximal relaxation between intact and endothelium-denuded preparations of rat aorta. In the presence of emodin (10 microM), the contractile responses of rat aorta to phenylephrine, serotonin and potassium chloride were depressed. The relaxation response to acetylcholine was attenuated by emodin, whereas that to isoproterenol was unaffected. The relaxation response to emodin was inhibited by free radical scavengers, superoxide dismutase, catalase and mannitol, and guanylate cyclase inhibitors, methylene blue and hemoglobin. Catalase was the most effective scavenger. Quinacrine (phospholipase A2 inhibitor), indomethacin (cyclooxygenase inhibitor) and nordihydroguaiaretic acid (NDGA, lipoxygenase inhibitor) potentiated the relaxation induced by emodin. NDGA was the most effective potentiator. Exposure of aortic rings to emodin (10 microM) increased the basal level of guanosine 3',5'-cyclic monophosphate (cGMP). It is suggested that the vasorelaxant effect of emodin may be mainly due to cGMP accumulation as a result of guanylate cyclase activation by free radicals and/or hydrogen peroxide generated from semiquinone.
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PMID:Vasorelaxant effect of emodin, an anthraquinone from a Chinese herb. 166 13


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