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)

Guanylate cyclase (GTP pyrophyosphate-lyase (cyclizing), EC 4.6.1.2) activity was examined in preparations from normal rat liver and a series of Morris hepatomas. Homogenate gyanylate cyclase activites were 3.2, 1.6 and 1.2 nmol cyclic GMP formed per min/g tissue ihe non-substrate analogs of IMP were weak inhibitors of this enzyme, GMP and four of its analogs had Ki values ranging from 30 to 80 muM. The GMP analogs (8-azaGMP, 7-deaza-8-azaGMP, 2'-dGMP and beta-D-arabinosylGMP) and GMP were competitive inhibitors with respect to GTP.
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PMID:Properties of guanylate cyclase in adult rat liver and several Morris hepatomas. 0 51

In a submaximal concentration carbachol contracted the rabbit colon muscle and increased the cyclic GMP level. The cyclic AMP level was reduced. In a Ca++-depleted muscle carbachol reduced the cyclic GMP level while the effect on the cyclic AMP content of the muscle was unchanged. Carbachol had no effect on the guanylate cyclase activity of the "plasma membrane fraction" (the 35-45% fraction). In the homogenate and the microsomal fractions Ca++ had no effect on the guanylate activity while it stimulated the enzyme in a soluble fraction. In the "plasma membrane fraction" cyclic GMP released Ca++ from the preloaded fraction and inhibited the Ca++ accumulation. These effects were not found in the vesicular microsomal fraction (the 35% fraction). In both fractions, however, cyclic GMP counteracted the stimulating effect of cyclic AMP. These results indicate that cyclic AMP and GMP may have antagonistic roles on the Ca++ metabolism in the colon muscle. It is suggested that cyclic GMP may act as some kind of positive feedback mechanism which may have a modulating effect on the release of Ca++ from one pool to another in rabbit colon.
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PMID:Effects of carbachol and calcium on the cyclic guanosine-3',5'-monophosphate (cyclic GMP) metabolism in intestinal smooth muscle. 1 81

Sarcolemma was isolated by fractionation of salt-extracted particles on two consecutive sucrose density gradients. Salt extraction of homogenates, rather than of washed particles, was found to preserve the activities of adenylate cyclase and ouabain-sensitive (Na+,-K+)-ATPase in the isolated sarcolemmal membranes. Purified sarcolemma contained substantial adenylate cyclase and guanylate cyclase activities that were stimulable by beta-adrenergic and muscarinic agonists, respectively. Significant ouabain-sensitive (Na+, K+)-ATPase activity as well as putative digitalis receptor activity was also present in sarcolemma. Cyclic nucleotide phosphodiesterases of sarcolemma, both cAMP- and cGMP-dependent, displayed positive cooperativity of substrate interactions; Ca2+ ions were found to increase the activity of the GMP-dependent enzyme.
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PMID:Isolation and enzymatic characterization of guinea pig cardiac sarcolemma. 2 1

A simple, sensitive and rapid technique is described, permitting separation of cGMP from GMP, GDP and GTP by the use of unidirectional high-voltage paper electrophoresis. The recovery of labeled cGMP in the assay of guanyl cyclase, by this procedure is 85-90%; the blank values (no enzyme) are negligible.
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PMID:High-voltage paper electrophoretic assay for guanyl cyclase. 2 92

Human CSF cyclic AMP and cyclic GMP have been measured as possible indicators of activity of central neurotransmitter-sensitive adenylate or guanylate cyclase. In an attempt to help to identify the specific neurotransmitter systems of origin of human CSF cyclic AMP and GMP, we studied Parkinson patients with and without L-dopa therapy and schizophrenic patients before and after propranolol therapy. No effect of L-dopa or propranolol was found on CSF cyclic nucleotides. However, Parkinson patients had a 40-50% reduction of CSF cyclic AMP and a 80-90% reduction of CSF cyclic GMP compared with the schizophrenic patients. Implications of this finding are discussed.
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PMID:The effect of L-dopa and propranolol on human CSF cyclic nucleotides. 21 Apr 80

HS-142-1, a specific nonpeptide antagonist for the atrial natriuretic peptide (ANP) receptor, equally blocked rat ANP (rANP)-, porcine brain natriuretic peptide-, or porcine C-type natriuretic peptide-stimulated GMP production in cultured bovine aortic smooth muscle (BASM) and bovine aortic endothelial (BAE) cells in a concentration-dependent fashion, at concentrations of 1-300 micrograms/ml. But, even at 300 micrograms/ml, HS-142-1 only weakly inhibited the specific binding of 125I-rANP to the BASM and BAE cells, where only a small portion of the binding sites are linked to guanylyl cyclase. Further, with BAE cell membranes, HS-142-1 recognized only the 135-kDa ANP receptor, which is thought from 125I-rANP affinity cross-linking studies to be the guanylyl cyclase-linked receptor. HS-142-1 also, if anything, inhibited the labeling of 135-kDa ANP receptors in the affinity cross-linking studies with BASM membranes, suggesting that a major portion of the 135-kDa ANP receptors are HS-142-1 insensitive and only a small portion of the 135-kDa ANP receptors are responsible for the blockade by HS-142-1 of GMP production in BASM cells. At a concentration of 100 micrograms/ml, HS-142-1 reversibly prevented ANP-induced relaxation of the isolated rabbit thoracic aorta induced to contract with 3 x 10(-7) M phenylephrine, but not the relaxation induced by sodium nitroprusside, isoproterenol, or papaverine. These results suggest that HS-142-1 specifically inhibits natriuretic peptide-induced vasorelaxation through the blockade of guanylyl cyclase-linked natriuretic peptide receptors. HS-142-1 thus will be a powerful tool for understanding the physiological roles, in vasculature, of natriuretic peptides, which contribute to the homeostasis of blood pressure and intravascular volume.
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PMID:Inhibition by HS-142-1, a novel nonpeptide atrial natriuretic peptide antagonist of microbial origin, of atrial natriuretic peptide-induced relaxation of isolated rabbit aorta through the blockade of guanylyl cyclase-linked receptors. 136 44

The effects of cyclic GMP on the release of calcium from intracellular stores, induced in murine peritoneal macrophages by either ATP or platelet-activating factor, were studied by microfluorimetry with fura-2. When macrophages were incubated for 10-20 min with 10 microM LY83583, an inhibitor of guanylate cyclase, the rise in intracellular calcium induced by agonist application was strongly depressed. This inhibition of the response to platelet-activating factor could be reversed by the addition of 0.1 mM cyclic 8-bromo-GMP. In the presence of cyclic 8-bromo-GMP, the decay of the calcium transient was speeded. Furthermore, when two calcium transients were evoked within 1 min by stimulating the cells with 10 microM ATP, the second calcium transient was more depressed than the first one in the presence of LY83583. These findings are compatible with the hypothesis that cyclic GMP is necessary for the activation of the calcium pump of the intracellular stores.
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PMID:Cyclic-GMP-dependent refilling of calcium stores in macrophages. 164 19

Histamine produces a rapid and massive increase of the c-GMP level of guinea-pig lung tissue. The EC50 value for this in vitro response is found to be 27 microM and the c-GMP level is maximally 9-fold elevated by 100 microM histamine. The response is stereoselectively inhibited by the enantiomers of chlorpheniramine, indicating H1-receptor involvement. Preincubation of lung tissue with 200 microM NCDC, a phospholipase C inhibitor, reduces the histamine (100 microM) responses to 16 +/- 3% (N = 6) of the control c-GMP production. Inhibition of protein kinase C by 50 microM H-7 does not significantly attenuate the H1-receptor response, whereas omittance of extracellular Ca2+ results in almost complete inhibition of the c-GMP production. The histamine-induced c-GMP response is inhibited by hemoglobin, methylene blue and the antioxidants butylated hydroxytoluene and nordihydroguaretic acid, indicating the involvement of a nitric oxide-dependent activation of soluble guanylate cyclase. This suggestion is supported by the concentration-dependent inhibition of the c-GMP production by NG-monomethyl-L-arginine (NMA). At a concentration of 20 microM NMA the histamine (100 microM) response is inhibited to 34 +/- 8% (N = 6) of the control response. This inhibition is reversed to 127 +/- 20% (N = 6) by the exogenous addition of 1 mM L-arginine. These findings show that after an initial H1-receptor-mediated, phospholipase C-dependent, Ca(2+)-mobilization the enzymatic conversion of L-arginine to nitric oxide is stimulated. This nitric oxide production is finally responsible for the activation of soluble guanylate cyclase, leading to the production of c-GMP.
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PMID:Histamine H1-receptor-mediated cyclic GMP production in guinea-pig lung tissue is an L-arginine-dependent process. 165 Feb 6

Guanylyl imidodiphosphate (GMP-PNP) hydrolyzing enzyme activity as a means of detecting plasma membrane guanylate cyclase was demonstrated in osteoblasts of chicken tibial metaphysis using a lead citrate histochemical method at the electron microscopic level. Activity was not discerned in osteoclasts or osteocytes. The reaction product development was completely abolished when the sections were incubated with substrate-free or MnCl2-free medium. Guanylate-(beta, gamma-methylene) diphosphate (GMP-PCP) was a less effective substrate than GMP-PNP, and Mn++ was a stronger stimulator than Mg++. No reaction product was observed on the plasma membrane of osteoblasts when beta-glycerophosphate or p-nitrophenylphosphate was used as substrate instead of GMP-PNP. The results implicate guanylate cyclase as a significant effector of osteoblast regulation at the site of the plasma membrane.
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PMID:Ultrastructural localization of guanylate cyclase in bone cells. 167 18

Light activation of cyclic GMP hydrolysis in rod outer segments is mediated by a G-protein which is active in the GTP-bound form. Substitution of GTP with a nonhydrolyzable GTP analogue is thought to leave the G-protein in a persistently activated state, thereby prolonging the hydrolysis of cyclic GMP. Restoration of cyclic GMP concentration in the cell also depends upon GTP since it is the substrate for guanylate cyclase, but little is known about the effects of GTP analogues on this enzyme. We report here the effects of the analogues of GTP and ATP as inhibitors and substrates of rod disk membrane guanylate cyclase. The rate of cyclic GMP synthesis from GTP in rod disk membranes was about 50 pmol min-1 (nmol of rhodopsin)-1. Analogues of GTP and adenine nucleotides competitively inhibited the cyclase activity. The order of inhibition, with magnesium as metal cofactor, was ATP greater than GMP-PNP greater than AMP-PNP approximately GTP-gamma-S; with manganese, AMP-PNP was more inhibitory than GTP-gamma-S. The inhibition constants, with magnesium as cofactor, were 0.65-2.0 mM for GTP-gamma-S, 0.4-0.8 mM for GMP-PNP, 1.5-2.3 mM for AMP-PNP, and 0.07-0.2 mM for ATP. The fraction of cyclase activity inhibited by analogues was similar at 1 and 0.03 microM calcium. Besides inhibition of cyclase, the analogues also served as its substrates. GTP-gamma-S substituted GTP with about 85% efficiency while GMP-PNP and ATP were about 5 and 7% as efficient, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions of nucleotide analogues with rod outer segment guanylate cyclase. 167 98


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