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)

Atrial natriuretic peptide (ANP) and sodium nitroprusside have potent vasodilator effects on the noradrenaline-precontracted isolated rabbit aorta. A distinct elevation of cyclic GMP in the aortic tissue was observed after both vasodilators. In contrast to sodium nitroprusside, ANP-(5-28) induced a dose-dependent cyclic GMP extrusion from the tissue into the medium. Thus, release of cyclic GMP appears to be specific for activation of particulate guanylate cyclase and provides a mechanism in addition to synthesis and degradation by which the cells can regulate their internal concentrations of cyclic GMP.
Eur J Pharmacol 1989 Dec 19
PMID:Different effects of ANP and nitroprusside on cyclic GMP extrusion of isolated aorta. 257 34

Release of nitric oxide (NO) from endothelial cells critically depends on a sustained increase in intracellular free calcium maintained by a transmembrane calcium influx into the cells. Therefore, we studied whether the free cytosolic calcium concentration directly affects the activity of the NO-forming enzyme(s) present in the cytosol from freshly harvested porcine aortic endothelial cells. NO was quantified by activation of a purified soluble guanylate cyclase co-incubated with the cytosol. In the presence of 1 mM L-arginine, 0.1 mM NADPH and 0.1 mM EGTA, endothelial cytosol (0.2 mg of cytosolic protein per ml) stimulated the activity of guanylate cyclase 5.0 +/- 0.5-fold (from 31 +/- 9 to 153 +/- 15 nmol cyclic GMP formed per min per mg guanylate cyclase). Calcium chloride increased this stimulation further in a concentration-dependent fashion by up to 136 +/- 15% (with 2 microM free calcium; EC50 0.3 microM). The calcium-dependent and -independent activation of guanylate cyclase was enhanced by superoxide dismutase (0.3 microM) and was inhibited by the stereospecifically acting inhibitor of L-arginine-dependent NO formation NG-nitro-L-arginine (1 mM) and by LY 83583 (1 microM), a generator of superoxide anions. Our findings suggest a calcium-dependent and -independent synthesis of NO from L-arginine by native porcine aortic endothelial cells.
Naunyn Schmiedebergs Arch Pharmacol 1989 Dec
PMID:Nitric oxide synthesis in endothelial cytosol: evidence for a calcium-dependent and a calcium-independent mechanism. 257 63

The cytosolic fraction of N1E-115 neuroblastoma cells catalysed the L-arginine- and NADPH-dependent formation of a substance that relaxed endothelium-denuded strips of rabbit aorta. Relaxations in response to this substance were enhanced in the presence of superoxide dismutase. N omega-Nitro-L-arginine and NG-monomethyl-L-arginine, two inhibitors of EDRF synthesis, markedly attenuated the relaxations. Hemoglobin, a scavenger of EDRF, and methylene blue, an inhibitor of soluble guanylate cyclase, completely abolished the relaxation to N1E-115 cytosol. In contrast, the cyclo-oxygenase inhibitor indomethacin did not alter the relaxations. These data demonstrate that the cytosol of a neuronally-derived cell line is able to synthesize a substance with pharmacological properties similar to EDRF.
Naunyn Schmiedebergs Arch Pharmacol 1989 Dec
PMID:The cytosol of N1E-115 neuroblastoma cells synthesizes an EDRF-like substance that relaxes rabbit aorta. 263 48

The recent discovery that mammalian cells can synthesize nitric oxide coincided with the identification of this simple gas as a factor involved in cellular communication. Nitric oxide has now been shown to be derived from L-arginine in macrophages, endothelial cells and possibly other cell types. Its physiological role in macrophages may be as a cytotoxic agent. However, nitric oxide produced by endothelial cells is thought to trigger vascular smooth muscle relaxation through activation of the enzyme guanylate cyclase.
Trends Biochem Sci 1989 Dec
PMID:Nitric oxide: biosynthesis and biological significance. 269 79

The regulation of guinea pig tracheal muscle tone by cyclic AMP-dependent and cyclic GMP-dependent relaxant mechanisms was investigated by studying the tracheal relaxant activities of forskolin, nitroprusside, N6-2'-O-dibutyryl-cyclic AMP and 8-bromoguanosine-cyclic GMP. In carbachol (3 X 10(-6) M)-contracted isolated tracheal rings, N6-2'-O-dibutyryl-cyclic AMP and 8-bromoguanosine-cyclic GMP each caused biphasic relaxation responses, which consisted of an acute relaxation followed by a sustained but lesser degree of relaxation. The biphasic nature of this response is suggested to result from a functional counter-balancing of cyclic nucleotide-dependent relaxant mechanisms and the contractile mechanisms stimulated by carbachol. The sensitivity of carbachol-contracted tracheal rings to forskolin and nitroprusside (activators of adenylate and guanylate cyclase, respectively) was generally not influenced by N6-2'-O-dibutyryl-cyclic AMP or 8-bromoguanosine-cyclic GMP in concentrations that induced up to 50% relaxation of the trachea. Furthermore, the partial relaxation of tracheal tension with one cyclic nucleotide analog did not alter the sensitivity of the tracheal rings to the other. These results demonstrate that cyclic AMP- and cyclic GMP-dependent mechanisms induce relaxations of the trachea that are functionally additive, each neither potentiating nor depressing the effects of the other. In the presence of 3 X 10(-6) M carbachol, the effectiveness of cyclic AMP- and cyclic GMP-dependent relaxant mechanisms appears to be fixed, and independent of the amount of active tension being maintained by the tracheal muscle itself.
J Pharmacol Exp Ther 1987 Dec
PMID:Co-regulation of tracheal tone by cyclic AMP- and cyclic GMP-dependent mechanisms. 282 52

Recent progress in understanding phototransduction has come primarily from studies on cell-free systems. To investigate the transduction process under physiological conditions, a fully functional preparation of retinal rod outer segments without attached inner segments was developed that allows electrical recording of light-sensitive current during intracellular dialysis with defined solutions. No light-sensitive current is recorded from detached outer segments dialyzed with nucleotide-free solutions, whereas cells detached from the retina into Ringer's solution containing 3-isobutyl-1-methyl-xanthine (a phosphodiesterase inhibitor) develop a light-sensitive inward dark current. This indicates that there is a basal level of cGMP-specific phosphodiesterase activity in the dark. Detached outer segments dialyzed with greater than or equal to 20 microM cGMP rapidly develop a light-suppressible current. A current of similar magnitude is generated more slowly during dialysis with a 50-fold greater concentration of GTP. Apparently, cGMP can be synthesized from GTP by guanylate cyclase in the outer segment. Cells dialyzed with cGMP alone show a reduced light sensitivity that is restored to normal by addition of 20 microM GTP. This action of GTP is antagonized by guanosine 5'-[beta-thio]diphosphate. These findings are in good agreement with biochemical evidence indicating that a GTP-binding protein (transducin) plays a pivotal role in the generation of responses to light. The recovery of photocurrent following a brief flash is delayed or abolished by dialysis with solutions that lack ATP or contain guanosine 5'-[gamma-thio]triphosphate, a nonhydrolyzable GTP analog. These results support the view that both GTP hydrolysis by activated transducin and ATP-dependent phosphorylation of a rhodopsin photoproduct are necessary for termination of the transduction process.
Proc Natl Acad Sci U S A 1987 Dec
PMID:Intracellular biochemical manipulation of phototransduction in detached rod outer segments. 282 76

The effects of isoproterenol, acetylcholine (Ach), and adenosine, on cyclic AMP (cAMP) and cyclic GMP (cGMP) contents were examined in chick hearts at various stages of embryonic development. The basal cAMP content was highest (87.7 +/- 1.3 pmol/mg protein) in young (3-day) embryonic chick hearts and decreased during development (9.6 +/- 0.6 pmol/mg protein in 9-19-day-old hearts). On the other hand, the cGMP content was lowest (45.5 +/- 2.3 fmol/mg protein) in young (3-day) embryonic chick hearts and increased during development (338 +/- 15.0 fmol/mg protein in 14-19-day-old hearts). Iso increased the cAMP concentration in embryonic hearts at all ages. Ach and Ado had no effect on the cAMP content at all ages. However, the Isoproterenol-induced stimulation of cAMP was inhibited by Ach and Adenosine at all ages. In young embryonic hearts, Ach and Ado increased cGMP concentration only slightly, whereas these agents caused a substantial increase in cGMP concentration in the older hearts. Thus, there was a clear age difference in the effects of Ach and Adenosine on the cGMP and cAMP concentrations. Nitroprusside and hydrogen peroxide increased cGMP concentration in older hearts (greater than 5-day-old) but not in the 3-day-old embryonic hearts. Thus, guanylate cyclase activity may be low in young (3-day-old) hearts. It summary, the cGMP level is very low in young embryonic chick hearts, and increases markedly during development. The changes in cGMP are reciprocal to those of cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)
J Dev Physiol 1987 Dec
PMID:Changes in cyclic nucleotide levels during embryonic development of chick hearts. 283 64

The influence of cyclic 3',5'-guanosine monophosphate (cGMP) on the lipolytic and antilipolytic (inhibition of glucagon-stimulated lipolysis) responses to GH (1 microgram/ml) was examined in chicken adipose tissue in vitro. Both 8-bromo-cGMP (0.1 mM) and sodium nitroprusside (1 mM) (a guanyl cyclase stimulator) completely inhibited the lipolytic effect of GH. A cGMP-lowering agent, LY83583 (10 microM), reversed the inhibitory effect of sodium nitroprusside on GH-stimulated lipolysis. Furthermore, the suppressive effects of insulin (100 ng/ml), insulin-like growth factor I (IGF-I) (100 ng/ml), or insulin-like growth factor II (IGF-II/MSA) (100 ng/ml), but not somatostatin (1 ng/ml), on GH-stimulated lipolysis were prevented by LY83583 addition. Neither 8-bromo-cGMP, sodium nitroprusside, nor LY83583 altered GH-induced inhibition of glucagon (1 ng/ml)-stimulated lipolysis. It is proposed that cGMP may mediate inhibitory control of GH-stimulated lipolysis by insulin, IGF-I, and IGF-II in chicken adipose tissue.
Proc Soc Exp Biol Med 1988 Dec
PMID:Inhibition of growth hormone-induced lipolysis by 3',5'-guanosine monophosphate in chicken adipose tissue in vitro. 284 72

We used an apparatus in which pieces of dark-adapted amphibian retinas (Rana pipiens, Bufo marinus) obtained under infrared illumination were exposed to precise intervals of 500-nm illuminations, and then frozen by contact of their outer segment surface with a liquid helium-cooled copper mirror. Sections of the frozen outer segment layer were obtained in a cryostat and then assayed for total extractable cyclic 3',5'-guanosine monophosphate (cGMP). Significant losses of cGMP with respect to the dark level were evident as early as 60 ms after light onset. With dim subsecond illuminations these losses were surprisingly large, which suggests a previously underestimated magnification in the cGMP cascade, or a transient substantial inhibition of guanylate cyclase activity in combination with increased cyclic GMP phosphodiesterase activity. Within the subsecond period, significant losses that were proportional to light intensity (2-log-unit range) and duration (60-550 ms) were generally not evident. However, losses significantly proportional to these factors became evident with durations of 1 s or longer. When pieces of retina were first illuminated (10 or 60 ms), then held in darkness for increasing periods before freezing, we observed a continuous loss of cGMP during the early postillumination dark period, followed by a recovery of the total cGMP level. The times for recovery to the preillumination level appear to be significantly longer than times reported for the recovery of the photoreceptor membrane potential after similar light exposures.
J Gen Physiol 1988 Dec
PMID:Light-induced losses and dark recovery rates of guanosine 3',5'-cyclic monophosphate in rod outer segments of intact amphibian photoreceptors. 285 Oct 28

1. The effects of aging on histamine-induced vasodilatation and cyclic GMP production in rat thoracic aorta were investigated. 2. This histamine-induced dilatation of the aorta was mediated by H1-receptors and was dependent on the endothelium. 3. Histamine induced the greatest dilatation of arteries of 3-4 week old rats, progressively less of those of rats of 8 to 56 weeks old, and scarcely detectable dilatation of those of 100 week old rats. 4. Histamine induced cyclic GMP production in aorta from rats of 4 weeks old, with no change in the cyclic AMP level. This increase in the cyclic GMP level induced by histamine also decreased with age, being about 70% as great at 8 weeks, 50% as great at 50-60 weeks, and 10% as great at 130 weeks of age. 5. Removal of the endothelium completely abolished the histamine-induced increase in cyclic GMP. 6. The dilator effect of nitroprusside, which enhances cyclic GMP production by stimulating guanylate cyclase directly (not indirectly via the endothelium derived relaxing factor, EDRF), also showed age-related attenuation. 7. The dilator effect of 8-bromo cyclic GMP, which stimulates cyclic GMP-dependent protein kinase, also decreased during aging. 8. These results suggest that aging reduces the ability of the endothelium to produce EDRF, which stimulates guanylate cyclase, and so decreases cyclic GMP production. Thus the decreased dilator response of the arteries to histamine during aging is probably due to both loss of endothelial function and reduction of guanylate cyclase activity. Alteration of cyclic GMP-dependent protein kinase activity may also participate in the age-related changes.
Br J Pharmacol 1988 Dec
PMID:Age-associated decrease in histamine-induced vasodilation may be due to reduction of cyclic GMP formation. 285 55


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