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)

Field stimulation of the non-adrenergic, non-cholinergic inhibitory nerves to the bovine isolated retractor penis muscle evoked a relaxation that was preceded by a rise in the tissue content of cyclic GMP. There was no change in the content of cyclic AMP. The selective cyclic GMP phosphodiesterase inhibitor, 2-o- propoxyphenyl -8- azapurin -6-one (M&B 22948), elevated the tissue's cyclic GMP content, and potentiated both the relaxation and the rise in cyclic GMP produced by inhibitory nerve stimulation. Sodium nitroprusside and an inhibitory factor extracted from the bovine retractor penis muscle mimicked the effects of inhibitory nerve stimulation in that they each produced relaxation associated with a selective rise in cyclic GMP concentration. Haemoglobin (in the form of erythrocyte haemolysate) and N- methylhydroxylamine , which are known to block guanylate cyclase, blocked the relaxation and the rise in cyclic GMP content produced by inhibitory nerve stimulation, inhibitory factor and sodium nitroprusside. Haemoglobin itself caused a rise in muscle tone and at the same time reduced the cyclic GMP content of the tissue. 8-Bromocyclic GMP, a permeant derivative of cyclic GMP, produced a relaxation of the muscle that, as expected, was not blocked by haemoglobin. Vasoactive intestinal polypeptide, prostaglandin E1 and forskolin each produced relaxation associated with a selective rise in cyclic AMP content. Their effects were not blocked by haemoglobin or N- methylhydroxylamine . It is concluded that inhibitory nerve stimulation in the bovine retractor penis muscle produces a relaxation that is mediated by cyclic GMP, although some substances relax the muscle without affecting cyclic GMP levels. The results are also compatible with the view that the extracts of muscle contain the inhibitory neurotransmitter.
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PMID:Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle. 632 22

Photoreceptor outer segments isolated from squid retina are known to contain a light-activated GTP-binding protein. Here it is shown that these photoreceptors contain around 0.01 mol cyclic GMP per mol rhodopsin. Adding GTP in the dark stimulates the production of 0.0003-0.001 mol cyclic GMP/mol rhodopsin per min. GTP and light cause a 2-fold faster increase in cyclic GMP. These results show that either (1) squid rhodopsin activates a guanylate cyclase, or (2) there is a constant guanylate cyclase activity and photoexcited rhodopsin inhibits a cyclic GMP phosphodiesterase.
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PMID:A light-stimulated increase of cyclic GMP in squid photoreceptors. 632 65

YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.
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PMID:YC-1, a novel activator of platelet guanylate cyclase. 752 71

3',5'-Cyclic guanosine monophosphate is the intracellular second messenger regulating phototransduction in mammals. The level of cGMP in photoreceptor cells is controlled by the cGMP-hydrolyzing enzyme cGMP phosphodiesterase and the cGMP-producing enzyme guanylate cyclase. Identification of a photoreceptor-specific guanylate cyclase (retGC) that may function in visual transduction was recently reported. As an initial step in assessing the potential for defects in the retGC (GUC2D) gene to be causal of hereditary retinal disease, we have determined its chromosome location. A 720-bp region of the human GUC2D locus was amplified with exon-specific primers. The amplified product contains three introns, two intact exons, and part of two additional exons, suggesting a high degree of structural complexity. PCR analysis of human-rodent somatic cell hybrids was used to map the GUC2D locus to chromosome 17. This assignment was confirmed and a more precise localization to 17p13.1 was obtained by fluorescence in situ hybridization.
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PMID:Human retinal guanylate cyclase (GUC2D) maps to chromosome 17p13.1. 780 40

To define the vasorelaxation mechanism of FK409, we examined the effect of the compound on vascular tension and cyclic nucleotide levels in isolated rat thoracic aorta contracted with norepinephrine, and on activities of guanylate cyclase and cyclic GMP phosphodiesterase prepared from rat or rabbit thoracic aorta. FK409 (1 x 10(-9) to 1 x 10(-6) M), like nitroglycerin (1 x 10(-9) to 1 x 10(-6) M), produced a potent vasorelaxant effect associated with an increase in cyclic GMP content of the tissue. There was no change in cyclic AMP levels. The vasorelaxant effect of FK409 was independent of the integrity of the endothelium, and was unaffected by L-NG-monomethylarginine (0.1 mM) or oxyhemoglobin (1 microM). On the other hand, FK409 (3.2 x 10(-7) M) activated soluble guanylate cyclase, and the activating effect was completely inhibited by oxyhemoglobin (10 nM). Cyclic GMP phosphodiesterase was unaffected by FK409 (1 x 10(-7) to 1 x 10(-5) M). Furthermore, in rat aortic soluble fraction FK409 (3 mM) was found to liberate nitric oxide (NO) which was evaluated spectrophotometrically after diazotization of sulfanilic acid and coupling with N-(1-naphthyl)-ethylenediamine. The liberation occurred even in the absence of L-cysteine (5 mM), in contrast to the case with nitroglycerin (3 mM). These results suggest that the vasorelaxant effect of FK409 is associated with an increase in intracellular cyclic GMP, and that the cyclic GMP accumulation is due to activation of soluble guanylate cyclase. The enzyme activation is probably due to NO released from the compound molecule in the vascular smooth muscle cells.
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PMID:Vasorelaxant mechanism of the new vasodilator, FK409. 790 Oct 40

The thoracic aorta was taken from nephrotic rats on the 40th day after a single i.v. injection of daunomycin (10 mg/kg). In the endothelium-intact aorta, the contractions induced by norepinephrine or B-HT 933, an alpha-2 adrenoceptor agonist, were significantly greater in nephrotic rats than in normal animals. However, such a difference was not observed in the KCl- or U46619-induced contractions. The difference in norepinephrine-induced contraction between nephrotic and normal preparations was enhanced by zaprinast, a cyclic GMP phosphodiesterase inhibitor. The contractions elicited by norepinephrine and B-HT 933 were potentiated by either removal of the endothelium or pretreatment with methylene blue, a guanylate cyclase inhibitor. The difference in the contractile response to these agonists between nephrotic and normal preparations was eliminated completely by either treatment. The cyclic GMP level in the endothelium-intact aorta in the presence of zaprinast was significantly lower in nephrotic rats than in normal animals. In the presence of zaprinast, norepinephrine, but not B-HT 933, caused an increase in the cyclic GMP level, which was abolished completely by pretreatment with prazosin, but not by yohimbine. These results suggest that the augmented contractile response to norepinephrine observed in nephrotic aorta may be due to the decrease in the stimulated release of endothelium-derived relaxing factor from the endothelial cells via the stimulation of endothelial alpha-1 adrenoceptors, whereas the augmented response to B-HT 933 may be due, at least in part, to the decrease in spontaneously released endothelium-derived relaxing factor.
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PMID:Nephrosis augments contractile response to adrenoceptor agonists by the decrease in release of endothelium-derived relaxing factor from the endothelial cells. 791 Feb 10

The effect of light adaptation on the period of photocurrent saturation induced by a bright stimulating flash was examined in rod photoreceptors of the larval-stage tiger salamander (Ambystoma tigrinum). Using suction electrodes, photocurrent responses to brief flashes were recorded from single, isolated rods in the presence and absence of steady background illumination. Background light decreased the saturation period (T) measured at fixed flash intensity (fixed If) and in this respect light-adapted the saturating response. Effects of the background on responses to weak (i.e. subsaturating) and bright flashes were compared with changes in a parameter, phi = e-delta T/TR*, where delta T is the decrease in saturation period, and where TR* is the slope of the line that relates T and ln If in a given state of adaptation. Dark- and light-adapted responses to flash intensities IDf and ILf, respectively, exhibited similar absolute peak photocurrent and falling-phase kinetics when IDf and ILf satisfied the relation, IDf = phi (ILf + IbTR*), where Ib is the background intensity. It is argued that phi approximates the relative PDE*/R* gain of transduction, i.e. the relative peak level of activated cGMP phosphodiesterase (PDE*) produced by a given, small amount of photoactivated visual pigment (R*). Interpreted on this view, the results imply that light adaptation derives largely from a decrease in PDE*/R gain, rather than from the stimulation of guanylate cyclase activity. The data are consistent with the possibility that modulation of the lifetime of PDE* underlies the background dependence of phi.
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PMID:Modulation of transduction gain in light adaptation of retinal rods. 801 83

Adrenergic stimulation of the adult pineal gland increases cAMP and cGMP production by over 100-fold. beta-Adrenergic stimulation results in Gs alpha-mediated cyclase activation; alpha 1-adrenergic activation potentiates the beta-adrenergic effects through mechanisms mediated by the intracellular Ca2+ concentration ([Ca2+]i) and Ca(2+)-phospholipid-dependent protein kinase. Development analysis of these responses has indicated that the adrenergic stimulation of cAMP is present several days after birth, but the cGMP response develops only after the second week of life. In the study presented here, the adrenergic-->cGMP response was analyzed in pineal glands from 10- and 25-day-old rats, with the intention of determining the basis of the developmental appearance of this response. Organ culture and tissue homogenate studies indicated that guanylate cyclase activity, cGMP phosphodiesterase activity, and adrenergic elevation of phospholipase-A2 were similar in pineal glands from 10- and 25-day-old rats. Norepinephrine stimulated an increase in [Ca2+]i in dispersed pinealocytes from 10-day-old rats, as has been previously demonstrated in adult pinealocytes. In contrast, several treatments that elevate [Ca2+]i had no effect on cGMP accumulation in forskolin-treated or beta-adrenergically activated glands from 10-day-old rats, but were fully effective in similarly treated glands from 25-day-old rats. However, glands from 10-day-old animals showed a 33-fold accumulation of cGMP when they were cultured together with glands from 25-day-old rats. These studies indicate that whereas many elements in the system that mediate adrenergic regulation of pineal cGMP are fully developed at 10 days of age, the developmental appearance of the cGMP response is triggered by the development of a process down-stream of the alpha 1-adrenergic stimulation of [Ca2+]i, and this process may involve a diffusible factor.
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PMID:Developmental appearance of pineal adrenergic-->guanosine 3',5'-monophosphate response is determined by a process down-stream from elevation of intracellular Ca2+: possible involvement of a diffusible factor. 809 11

Electrical field stimulation (EFS) induced a relaxation response in female rabbit urethral smooth muscle strips precontracted with phenylephrine. The relaxation response was inhibited by tetrodotoxin, but not by atropine, propranolol, or hexamethonium. Thus, the relaxation response results from stimulation of inhibitory non-adrenergic, non-cholinergic nerves. The EFS induced relaxation response was inhibited by an inhibitor of nitric oxide biosynthesis, NG-nitro-L-arginine. This inhibition was overcome by addition of a precursor of nitric oxide, L-arginine. An inhibitor of soluble guanylate cyclase, methylene blue, but not an inhibitor of soluble adenylate cyclase, SQ22536 reduced the relaxation response. And a selective cyclic GMP phosphodiesterase inhibitor, M & B 22948 and also a non selective phosphodiesterase inhibitor, 3-isobutyl-1-methyl xanthine, potentiated the relaxation response. Cyclic GMP, but not cyclic AMP contents were significantly elevated by EFS in urethral smooth muscle strips. These data demonstrate that agents which affect the biosynthesis of nitric oxide are associated with the urethral relaxation evoked by EFS, and that cyclic GMP but not cyclic AMP mediates the relaxation response.
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PMID:[Roles of cAMP and cGMP on non-adrenergic, non-cholinergic relaxation in rabbit urethral smooth muscle]. 812 Nov 15

In rat aorta, KT2-734 inhibited contractile responses to 5-hydroxytryptamine (5-HT) and KCl. KT2-734 inhibited the relaxing effect of verapamil, but not nifedipine. Similarly, verapamil, but not nifedipine, inhibited the vasorelaxing effect of KT2-734. KT2-734 relaxation was inhibited by endothelium removal but not by atropine and propranolol. Methylene blue, a guanylyl cyclase inhibitor, and NG-monomethyl arginine also inhibited the relaxation both in the presence and absence of endothelium. In the absence of endothelium, KT2-734 potentiated the relaxation induced by L-arginine, nitroglycerin and isoproterenol. In addition, M & B 22,948, a cGMP phosphodiesterase inhibitor, and theophylline inhibited and potentiated, respectively, KT2-734-induced relaxation. However, methylene blue inhibited the potentiation of isoproterenol relaxation by KT2-734 and that of KT2-734-relaxation by theophylline. KT2-734 caused increases in the level of cGMP without significantly affecting the cAMP level. These results suggest that KT2-734 may cause endothelium-independent relaxation mainly due to inhibition of cGMP-phosphodiesterase.
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PMID:Vasoinhibitory action of KT2-734, an antihypertensive agent, in isolated rat aorta. 813 65


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