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 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.
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PMID:Inhibition of growth hormone-induced lipolysis by 3',5'-guanosine monophosphate in chicken adipose tissue in vitro. 284 72

Tolbutamide and its non-hypoglycemic analog carboxytolbutamide increased soluble and particulate guanylate cyclase [E.C.4.6.1.2] activity twofold in liver, lung, colon, pancreas, kidney cortex, heart and spleen at a concentration of 1 microM. The ED50 for stimulation of guanylate cyclase activity was 50 nM for both agents. No stimulation of guanylate cyclase activity was observed with either agent when their concentrations were decreased to 1 nM. Maximal enhancement was at a concentration of 100 nM for both agents. Butylated hydroxytoluene, an antioxidant and hydroxyl radical scavenger, completely blocked any enhancement of guanylate cyclase by carboxytolbutamide, suggesting that its effect was due to a nonspecific oxidation reaction. Tolbutamide's augmentation of guanylate cyclase activity was not blocked by butylated hydroxytoluene. Varying the concentration of the guanylate cyclase co-factor manganese indicated that these sulfonylureas could not maximally activate guanylate cyclase without manganese being present. In addition to increased insulin receptors in monocytes and fibroblasts, the present findings, plus similar findings with the oral hypoglycemic agent glibenclamide, may help explain the mechanism of the extra-pancreatic effects of oral sulfonylurea agents at the cellular level.
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PMID:The comparative effects of tolbutamide and the non-hypoglycemic analog carboxytolbutamide on guanylate cyclase activity. 286 85

In the membranous signal transduction process, hormone-binding to receptors causes receptor interaction with signal-transducing components; these components transfer the stimulus to effector systems, which generate intracellular signals. Several guanine nucleotide-binding proteins (N- or G-proteins) have been identified as membranous signal-transducing components. Two N-proteins are involved in the hormonal regulation of adenylate cyclase activity, one of which being stimulatory (Ns), the other one being inhibitory (Ni). Ns, Ni and a third N-protein, No, whose function is unknown, occur ubiquitously. On the other hand, transducin, an N-protein, which functionally couples light-activated rhodopsin to a cGMP phosphodiesterase, is specific for the retina. In addition to their established role as transducers regulating adenylate cyclase and retinal cGMP phosphodiesterase, N-proteins proteins may be involved in two mechanisms by which the cytoplasmic calcium concentration is elevated, i.e. hormonal stimulation of a phospholipase C catalyzing phosphatidyl-inositol 4,5-diphosphate hydrolysis (Pi response) and hormone-induced opening of receptor-operated calcium channels; the membrane-bound forms of cAMP phosphodiesterase and guanylate cyclase, stimulated by insulin and atrial natriuretic factor, respectively, are also likely to be regulated via N-proteins. Guanine nucleotide-binding proteins appear to play a universal role in transmembranous signalling processes, controlling effector systems (i.e. enzymes and ion channels) that regulate cytoplasmic concentrations of intracellular messengers such as cyclic AMP, cyclic GMP and calcium.
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PMID:[Principles of transmembranous signal transduction in the action of hormones and neurotransmitters]. 286 63

Patients with leprechaunism have hyperinsulinemia and extreme insulin resistance. The mechanism of the insulin resistance has not been delineated. To examine postreceptor events in this unusual syndrome we have assayed the enzyme guanylate cyclase [E.C.4.6.12], which is modulated by insulin, and the concentration of the intracellular messenger cyclic GMP in liver from two children with leprechaunism and extreme insulin resistance. Both patients exhibited down regulation of the red blood cell insulin receptors, but normal insulin receptor binding to Ebstein-Barr transformed IM-9 lymphocytes and monocytes. There was no evidence of antireceptor or antiinsulin antibodies. Activity of liver guanylate cyclase expressed as pmol/mg protein/10 min incubation in the soluble and particulate fractions were, respectively, Ark-1 133 +/- 18, 25 +/- 6; Ark-2 129 +/- 17, 23 +/- 8; control children (six average) 287 +/- 16, 55 +/- 9. The concentration of cyclic GMP was also 50% lower (0.08 +/- 0.03 in Ark-1 and 0.07 +/- 0.04 in Ark-2), compared to 0.19 +/- 0.07 pmol/mg protein/min in the control livers. There was no change in adenylate cyclase activity in children with leprechaunism versus the control children. These data suggest an abnormality of a postreceptor event in this rare genetic disease. These data, however, do not rule out that in some cases of leprechaunism a receptor binding abnormality may be the primary defect. We speculate that a defect in insulin action distal to plasma membrane receptor binding may be etiological in this unusual syndrome.
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PMID:Decreased cyclic guanosine 3',5' monophosphate and guanylate cyclase activity in leprechaunism: evidence for a postreceptor defect. 287 43

Atrial natriuretic factor (ANF) specifically stimulated the endogenous phosphorylation of a protein band in an isolated membrane fraction of human placenta. The apparent molecular weight of the substrate protein as determined by SDS-polyacrylamide gel electrophoresis is 160-170,000. In the same membrane fraction, ANF also stimulated guanylate cyclase activity in a dose-dependent manner. Guanosine 3':5'-cyclic monophosphate (cyclic GMP), added to the membrane fraction in lieu of ANF, also stimulated the phosphorylation of several protein bands, one of which have the same apparent molecular weight as the one stimulated by ANF. In contrast, adenosine 3':5'-cyclic monophosphate (cyclic AMP) at a similar concentration and hormones such as angiotensin II, insulin and vasopressin had no effect on the phosphorylation state of this protein band. The finding that ANF alters the phosphorylation state of a certain membrane protein and that this effect is mimicked by cyclic-GMP suggests that at least some of the biological action of ANF may be mediated by the phosphorylation of membrane protein involving a cyclic GMP-dependent protein kinase.
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PMID:Atrial natriuretic factor induced phosphorylation of human placental membrane protein: an effect mimicked by guanosine 3':5'-cyclic monophosphate. 287 3

Insulin imprinting of Tetrahymena pyriformis in different growth phases had been investigated. Cells formed in the early logarithmic phase (18-hour culture) showed enhanced hormone binding at the second encounter with the hormone proving that imprinting had developed. This phenomenon was not observed in cells formed in the late logarithmic phase (42-hour culture) or in the stationary phase (66-hour culture). Lipid transformation processes, alteration of the guanyl cyclase activity and enhanced cell division may be responsible for this effect. Cell-growth phase G1 was especially favourable for development of imprinting.
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PMID:Age of the cell culture: a factor influencing hormonal imprinting of Tetrahymena. 288 56

Rat liver regeneration is regulated by a humoral signal that includes insulin and a sustained elevation in glucagon. The intracellular response is characterized by a rise in cAMP as well as altered cGMP metabolism, i.e. increased particulate guanylate cyclase activity. To evaluate the role of hormones in the regulation of guanylate cyclase during liver regeneration, the enzyme activity of primary cultures of rat hepatocytes was examined. Hepatocytes were maintained for 22 h in medium containing various combinations of insulin, glucagon, and cAMP. The cells were then harvested and homogenized and the guanylate cyclase activity was assessed in vitro. Hepatocytes maintained in 100 nM insulin exhibited a 42% (p < 0.001) increase in guanylate cyclase activity when compared to cells cultured in medium alone. Incubation with glucagon (100 nM) produced a 52% (p < 0.01) rise. In the presence of insulin (100 nM), culturing with as little as 5 nM glucagon resulted in increased activity, and 100 nM glucagon produced a 161% (p < 0.001) rise above cultures maintained in insulin alone. Thus, the combination of the two hormones produced an effect that was significantly (p < 0.01) greater than additive. Dibutyryl cAMP and 8-bromoadenosine 3':5'-monophosphoric acid were at least as effective as glucagon; the enzyme activity of cells maintained in 5 microM N6,02'-dibutyryl adenosine 3':5'-monophosphoric acid and 100 nM insulin was 243% (p < 0.001) above those in insulin alone. The findings suggest that the activity of hepatocyte guanylate cyclase is regulated by a synergistic action of insulin and glucagon and that positive interactions between the two cyclic nucleotide second messenger systems exist.
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PMID:The role of insulin, glucagon, and cAMP in the regulation of hepatocyte guanylate cyclase activity. 610 19

Somatostatin has been shown to inhibit the release of various polypeptide hormones including insulin, glucagon, gastrin, thyroid stimulating hormone, and growth hormone. The mechanism by which somatostatin inhibits the release of these various polypeptide hormones has not been fully elucidated. It has been reported that somatostatin increases the level of the second messenger cyclic GMP in rat brain and in the anterior pituitary gland. The present investigation was designed to determine if these responses seen in the anterior pituitary gland and brain were due to activation of guanylate cyclase [GTP-pyrophosphate lyase (cyclizing), E.C.4.6.1.2.], the enzyme that catalyzes the formation of cyclic GMP. Somatostatin at a concentration of 2 pM enhanced guanylate cyclase activity two-fold in rat cerebrum and anterior pituitary gland. This enhancement of guanylate cyclase activity was also seen in rat liver, pancreas, stomach, and small intestine at the same concentration of somatostatin. Increasing the concentration of somatostatin to 20 microM, caused a marked inhibition of guanylate cyclase activity in all these tissues. Dose-reponse curves done on gastric guanylate cyclase activity revealed that over a concentration range of 2 pM to 0.2 microM, somatostatin had a stimulatory effect on guanylate cyclase activity while at concentrations above 10 microM somatostatin was inhibitory to guanylate cyclase activity. The biphasic pattern of enhancement of guanylate cyclase activity at lower concentrations of somatostatin and inhibition at higher concentrations may help to explain some of the discrepancies seen with previous investigations with somatostatin, hormone release, and cyclic nucleotide metabolism.
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PMID:The interrelationship of somatostatin and guanylate cyclase activity. 611 Jan 70

Twelve hyperglycemic, glycosuric, and ketonuric Djungarian hamsters with average blood glucose concentrations of 295+-32 mg/dl were compared to twelve non-glycosuric, but ketonuric Djungarian hamsters with average blood glucose concentrations of 88+-11 mg/dl with regards to their cyclic nucleotide metabolism. The glycosuric Djungarian hamsters had decreased guanylate cyclase (E.C.4.6.1.2.) activity in vitro and cyclic GMP levels in vivo in liver, lung, kidney, colon, heart, spleen, and pancreas that was approximately 50% of the guanylate cyclase activity in these same tissues of non-glycosuric Djungarian hamsters. The decreased tissue guanylate cyclase activity and cyclic GMP levels in the glycosuric animals could be restored to the level of non-glycosuric Djungarian hamsters with 100 U regular insulin, but not with 50 or 10 U of regular insulin. Fifty and 100 U of regular insulin also increased the level of guanylate cyclase activity in the non-glycosuric (control) animals. There was no change in adenylate cyclase (E.C.4.6.1.1.) activity but there were increased cyclic AMP levels in the glycosuric when compared to the non-glycosuric Djungarian hamsters that were correctable with 100 U of insulin. We conclude that guanylate cyclase activity is decreased in the peripheral tissues of glycosuric Djungarian hamsters as compared to non-glycosuric Djungarian hamsters and that insulin modulates this enzyme.
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PMID:Decreased tissue guanylate cyclase activity in glycosuric Djungarian hamsters (Phodopus sungorus) that is correctable with insulin. 612 Jan 35

Glibenclamide enhanced the activity in the rat of guanylate cyclase in a number of extra-pancreatic tissues. Thus, glibenclamide enhanced guanylate cyclase activity in vitro two- to threefold in liver, kidney, heart, spleen and colon at a concentration of 1 mumol/l. Dose-response curves of glibenclamide on hepatic guanylate cyclase revealed that more than half-maximal stimulation was observed at a concentration as low as 10 nmol/l (p less than 0.001) and no stimulation of guanylate cyclase was seen when the concentration was decreased to 1 nmol/l. Maximal enhancement was seen at 100 nmol/l of glibenclamide. Varying the concentration of the guanylate cyclase co-factor manganese had no effect on the glibenclamide enhancement of guanylate cyclase. In addition to the increased insulin receptors found recently in monocytes and fibroblasts, the present findings may help explain the extra-pancreatic effects of glibenclamide and possibly of other sulphonylurea drugs.
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PMID:Direct effect of glibenclamide on guanylate cyclase activity in the rat in vitro. 612 72


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