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)

The mechanism of cholinergic stimulation of alanine and glutamine formation and release from skeletal muscle was studied using rat epitrochlaris preparations. The increased alanine and glutamine release produced by carbamylcholine (10(-6) M) was reproduced by tetramethylammonium (10(-6) M) but not by pilocarpine (10(-6) M) and was blocked by hexamethonium (10(-4) M) but not by atropine (10(-7) M). This increased alanine and glutamine release was not associated with altered muscle cAMP levels. However, carbamylcholine (10(-6) M) and tetramethylammonium (10(-6) M) did not increase levels of cGMP, 134% and 101%, respectively, and these increments in cGMP were blocked by hexamethonium but not by atropine. Carbamylcholine produced a concentration-dependent increase in cGMP levels. Methylisobutylxanthine and theophylline augmented the increased amino acid release and increased cGMP levels produced by carbamylcholine. Neither xanthine derivative alone altered alanine and glutamine release or cyclic nucleotide levels. Added cGMP increased amino acid release and the uptake of [U-14C]alanine and alpha-amino[14C]isobutyric acid. Carbamylcholine did not alter muscle phosphorylase a activity, glycogen levels, or basal adenylate cyclase activity. These data indicate that cholinergic stimulation of muscle alanine and glutamine formation and release involves a nicotinic cholinergic receptor and may be mediated by increased levels of cGMP, which in turn may result from a cholinergic stimulation of muscle guanylyl cyclase.
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PMID:Cholinergic stimulation of skeletal muscle alanine and glutamine formation and release. Evidence for mediation by a nicotinic cholinergic receptor and guanosine 3':5'-monophosphate. 8 Dec 8

The pyruvate-stimulated adenylate cyclase from Brevibacterium liquefaciens produces up to 450 microM cyclic AMP in the culture medium when the bacterium is grown on glucose and alanine. In this paper we report the cloning, expression and sequencing of the gene for this enzyme. Residues were identified, within the C-terminal domain, which are conserved in adenylate and guanylate cyclase sequences from eukaryotes and in the adenylate cyclase of the prokaryote Rhizobium meliloti. We have also identified a sequence of 30 residues near the N-terminus of the protein which is homologous to part of the regulatory domain of the cellular homologues of the oncogenes fes and fps; this sequence is also present in the avian Fujinami sarcoma virus fps gene.
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PMID:A pyruvate-stimulated adenylate cyclase has a sequence related to the fes/fps oncogenes and to eukaryotic cyclases. 168 68

The amino acid L-arginine is a precursor of endothelium derived relaxing factor (EDRF). The pentapeptide 6A (Ala-Arg-Pro-Ala-Lys) released by plasmin degradation of fibrinogen also contains arginine and relaxes vascular smooth muscle by releasing EDRF (nitric oxide). To determine and compare the effects of L-arginine, peptide 6A and a combination of L-arginine and peptide 6A on femoral artery blood flow and vascular resistance, anesthetized mongrel dog were administered saline, L-arginine, D-arginine, peptide 6A and L-arginine + peptide 6A in a random order. L-arginine and peptide 6A both induced an immediate dose-dependent short-lasting increase in femoral blood flow and a decrease in vascular resistance. Peptide 6A exerted a much greater (P less than 0.01) vasodilatory effect than did L-arginine at the same molar concentration suggesting that properties besides the arginine content are important in the effect of the pentapeptide. D-arginine had much less effect than L-arginine, indicating that the effect of L-arginine may be related to its utilization for synthesis of EDRF. When the peptide 6A was given soon after L-arginine, its effect on blood flow was not greater than that of L-arginine alone suggesting that L-arginine in a large amount makes guanylate cyclase less available for the more active peptide.
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PMID:Effect of L-arginine and an arginine-containing pentapeptide on canine femoral arterial blood flow. 177 15

This study shows that stimulating bone marrow-derived macrophages with either lipopolysaccharide (LPS) or the lipopeptide N-palmitoyl-S-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-(R)- cysteinyl-alanyl-glycine (Pam3Cys-Ala-Gly), a synthetic analogue of the N-terminal part of bacterial lipoprotein, leads to the formation of nitric oxide (NO) and nitrite (NO2-), a stable analogue of NO. NO was detected by applying the chemiluminescence method and by measuring the activity of exogenously added soluble guanylate cyclase (GC), which is strongly and selectively activated by NO. Synthesis of NO and NO2- occurs via activation of the L-arginine and NADPH-dependent enzyme(s) present in the cytosol of bone marrow-derived macrophages. No produced by this non-constitutive L-arginine pathway is thought to be responsible for the cytostatic and killing properties of macrophages (Stuehr & Nathan, 1989). Macrophages stimulated either with LPS or Pam3Cys-Ala-Gly exhibited a 6-hr lag time before engaging in nitrite synthesis, a time at which expression of the NO-forming enzyme had already reached its maximum. The regulation of NO and NO2- synthesis during macrophage development seems to differ from that of cytokine synthesis. Whereas cytokine release varies during a culture period up to 20 days, NO synthesis and expression of the NO-forming enzyme remain unaltered. These studies show that, similar to LPS, Pam3Cys-Ala-Gly is a potent activator of 'the oxidative L-arginine pathway' in bone marrow-derived macrophages. Whether both stimuli use the same signal transfer mechanism to induce this pathway and whether NO synthesized by this pathway is involved in the activation of the enzyme guanylate cyclase in macrophages requires clarification.
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PMID:L-arginine-dependent nitric oxide formation and nitrite release in bone marrow-derived macrophages stimulated with bacterial lipopeptide and lipopolysaccharide. 197 43

The response to small peptides such as Arg-vasopressin, oxytocin and tachykinins was investigated in cultured porcine aortic endothelial cells. The production of endothelium-derived nitric oxide was assessed indirectly by the accumulation of cyclic GMP, a response that is due to the increased activity of soluble guanylate cyclase of the endothelial cells after release of the mediator. Arg-vasopressin, oxytocin, substance P and physalae-min (an analog of substance P, pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-Gly-Leu-Met-NH2) markedly and transiently stimulated the production of cyclic GMP without affecting that of cyclic AMP. Treatment of endothelial cells with either hemoglobin or methylene blue reduced significantly both the basal and stimulated level of cyclic GMP. The production of cyclic GMP evoked by Arg-vasopressin and substance P was inhibited selectively by NG-monomethyl-L-arginine but not by its D-enantiomer. The neurohypophyseal hormones and related peptides stimulated the accumulation of cyclic GMP in a concentration-dependent manner, with the following relative order of potency: oxytocin greater than Lys-vasopressin greater than Arg-vasopressin much greater than [deamino-Cys1, D-Arg8]-vasopressin. The production of cyclic GMP evoked by oxytocin was inhibited selectively by [d(CH2)5, Tyr(OMe)2, Orn8]-vasotocin, an oxytocin antagonist. The production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin was inhibited by [beta-mercapto-beta, beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8]-vasopressin, a selective V1-receptor antagonist. The moderate production of cyclic GMP evoked by [deamino-Cys1, D-Arg8]-vasopressin was inhibited significantly by the V1-receptor antagonist. The peptide antagonists affected only minimally or not at all the production of cyclic GMP evoked by a donor of nitric oxide, SIN-1 (3-Morpholino-Sydnonimine). These observations indicate that 1) neurohypophyseal hormones and tachykinins stimulate the accumulation of cyclic GMP in cultured porcine aortic endothelial cells by increasing the production of endothelial-derived nitric oxide, which in turn enhances the activity of soluble guanylate cyclase; 2) the production of cyclic GMP in response to oxytocin is due to activation of oxytocinergic receptors; and 3) the production of cyclic GMP evoked by Arg-vasopressin and Lys-vasopressin is due mostly to activation of V1-vasopressinergic receptors.
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PMID:Neurohypophyseal peptides and tachykinins stimulate the production of cyclic GMP in cultured porcine aortic endothelial cells. 217 9

Met-enkephalin (ME) exerts a bimodal effect on functional activities of rat peritoneal macrophages (PM); in a range of low concentration (10(-9)-10(-7)M) antibody dependent cellular cytotoxicity (ADCC) was markedly stimulated with a simultaneous decrease of Fc gamma receptor (Fc gamma R) medicated phagocytosis while the opposite was observed at 10(-6)-10(-5)M concentrations. Studying the possible underlying mechanism(s) the followings were recorded: (1) ME in all applied concentrations induced an early Na+ influx which was followed by a Ca2+ efflux in the range of low concentrations. In the range of high concentrations Na+ influx was accompanied by a Ca2+ influx. (2) ME at 10(-8) M concentration induced a rise in cGMP level with a plateau in the 60-120th min of incubation. This effect was prevented by 10(-5) M of naloxone. At 10(-6) M concentration a transient rise of cAMP level was recorded which was not affected by naloxone. (3) Verapamil in 10(-6) M abolished both the Ca2+ influx and the rise in cAMP level induced by 10(-6)-10(-5) M ME but not the rise in cGMP level induced by lower ME concentrations. (4) cAMP elevation by high ME concentrations was abolished by enkephalinase inhibitory puromycin. (5) PM-enkephalinase as assessed by the cleavage of fluorogenic substrate L-alanine beta naphthylamide (ABNA), was inhibited by 10(-6)-10(-5) M of ME. This inhibition was abolished by verapamil, but not affected by naloxone. In the range of low concentrations ME appears to act on specific delta opioid receptors and its action is positively coupled to guanylate cyclase. In relatively higher concentrations ME-action is not mediated by specific delta opioid receptors and it appears to involve Ca2+ influx, adenylate cyclase activation as well as the processing of hormone by PM-enkephalinase.
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PMID:Bidirectional effect of met-enkephalin on macrophage effector functions. 242 Nov 52

Two peptides, speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) and resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2), which activate sperm respiration and motility and elevate cyclic GMP concentrations in a species-specific manner, were tested for effects on guanylate cyclase activity. The guanylate cyclase of sea urchin spermatozoa is a glycoprotein and it is localized entirely on the plasma membrane. When intact sea urchin sperm cells were incubated with the appropriate peptide for time periods as short as 5 s and subsequently homogenized in detergent, guanylate cyclase activity was found to be as low as 10% of the activity of cells not treated with peptide. The peptides showed complete species specificity and analogues of one peptide (speract) caused decreases in enzyme activity coincident with their receptor binding properties. The peptides did not inhibit enzyme activity when added after detergent solubilization of the enzyme. When detergent-solubilized spermatozoa were incubated at 22 degrees C, guanylate cyclase activity declined in previously nontreated cells to the peptide-treated level. The rate of decline was dependent on temperature and protein concentration. When spermatozoa were first incubated with 32P, the decrease in guanylate cyclase activity was accompanied by a shift in the apparent molecular weight of a major plasma membrane protein (160,000-150,000) and a loss of 32P label from the 160,000 band. Other agents (Monensin A, NH4Cl) which were capable of stimulating sperm respiration and motility also caused decreases of guanylate cyclase activity when added to intact but not detergent-solubilized spermatozoa. The maximal decrease in guanylate cyclase activity occurred 5-10 min after addition of these agents. The enzyme response to Monensin A required extracellular Na+ suggestive that the ionophore caused the effect on guanylate cyclase activity by virtue of its ability to catalyze Na+/H+ exchange. These studies demonstrate that guanylate cyclase activity of sperm cells can be altered by the specific interaction of egg-associated peptides with their plasma membrane receptors.
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PMID:Receptor-mediated regulation of guanylate cyclase activity in spermatozoa. 286 Dec 1

The sea urchin egg peptides speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly) and resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Arg-Leu-NH2) bind to spermatozoa of the homologous species (Lytechinus pictus or Arbacia punctulata, respectively) and cause transient elevations of cyclic GMP concentrations (Hansbrough, J. R., and Garbers, D. L. (1981) J. Biol. Chem. 256, 1447-1452). The addition of these peptides to spermatozoan membrane preparations caused a rapid and dramatic (up to 25-fold) activation of guanylate cyclase. The peptide-induced activation of guanylate cyclase was transient, and the subsequent decline in enzyme activity coincided with conversion of a high Mr (phosphorylated) form of guanylate cyclase to a low Mr (dephosphorylated) form. When membranes were incubated at pH 8.0, the high Mr form was converted to the low Mr form without substantial changes in basal enzyme activity. However, the peptide-stimulated activity of the low Mr form of guanylate cyclase was much less than the peptide-stimulated activity of the high Mr form. Activation of the low Mr form by peptide was not transient and persisted for at least 10 min. In addition, the pH 8.0 treatment that caused the Mr conversion of guanylate cyclase also caused an increase in the peptide-binding capacity of the membranes. We propose a model in which activation of the membrane form of guanylate cyclase is receptor-mediated; the extent of enzyme activation is modulated by its phosphorylation state.
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PMID:Receptor-mediated activation of spermatozoan guanylate cyclase. 287 90

GGGYG-resact (Gly-Gly-Gly-Tyr-Gly-Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg -Leu-NH2) was synthesized and shown to possess the same respiration-stimulating activity and receptor-binding ability as resact. The incubation of intact sperm cells with radioiodinated peptide, 125I-GGGYG-resact, and the chemical cross-linking reagent, disuccinimidyl suberate, resulted in the appearance of a single, major radioactive band of apparent molecular weight 160,000 (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The interaction was specific since 150 nM nonradioactive resact but not speract (200 nM) blocked formation of the radioactive band. The radioactive, cross-linked protein co-migrated with 32P-labeled guanylate cyclase and could be immunoprecipitated with a polyclonal antibody raised in rabbits against the sperm guanylate cyclase. The incubation of intact cells with NH4Cl resulted in the partial dephosphorylation of guanylate cyclase and a change in its apparent molecular weight from 160,000 to 150,000; NH4Cl also caused the same conversion in the apparent molecular weight of the cross-linked protein. These data demonstrate that an analogue of resact can be covalently coupled to guanylate cyclase with the specificity predicted for the peptide receptor.
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PMID:Covalent coupling of a resact analogue to guanylate cyclase. 287 82

Speract (Gly-Phe-Asp-Leu-Asn-Gly-Gly-Gly-Val-Gly), a peptide obtained from the culture medium of Strongylocentrotus purpuratus eggs, stimulates the respiration and motility of S. purpuratus spermatozoa under appropriate conditions. Resact (Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-LeuNH2), a peptide obtained from Arbacia punctulata eggs also stimulates the metabolism and motility of A. punctulata spermatozoa, however, it fails to stimulate S. purpuratus spermatozoa. Early biochemical responses of the spermatozoa to the egg peptides include a net H+ efflux and elevations of cyclic AMP and cyclic GMP concentrations. In addition, in A. punctulata spermatozoa, a major plasma membrane protein is modified in response to resact such that its apparent molecular weight shifts from 160,000 to 150,000. If cells are incubated with 32P, the 160,000 molecular weight form of the protein becomes radiolabeled; subsequent addition of resact causes a rapid loss of 32P from the protein. The plasma membrane protein appears to be the enzyme, guanylate cyclase; coincident with the shift in apparent molecular weight, enzyme activity decreases by as much as 90%. Since speract fails to cause these responses in A. punctulata, it can be concluded that the events are receptor-mediated.
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PMID:Peptides associated with eggs: mechanisms of interaction with spermatozoa. 288 30


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