Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Particulate guanylate cyclase from rat lung was stimulated less than 2-fold by agents capable of activating the soluble guanylate cyclase, including sodium nitroprusside, MNNG, azide and hydroxylamine. The action of the first two agents was potentiated by 10 mM 2-mercaptoethanol, and that of the last two by catalase. Pretreatment of the particulate enzyme with the polyene antibiotic, filipin, potentiated the stimulatory effects of the activators, activity with 1 mM nitroprusside in the presence of 2-mercaptoethanol being increased 10.4-fold over basal. The enzyme treated with filipin and nitroprusside showed less specificity for Mn2+, as it was able to use Mg2+ as sole cation more efficiently than the untreated enzyme. Since filipin is known to alter membrane fluidity by interacting with membrane cholesterol, it is proposed that the activity of membrane bound guanylate cylase may be regulated in part by the fluid state of the phospholipid matrix.
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PMID:Activation of particulate guanylate cyclase by nitroprusside and MNNG after filipin treatment. 4 Oct 6

Dynamic changes in total glucose utilization in isolated islets of Langerhans of the rat were determined by quantitation of the formation of 3H2O from D-[5-3H]glucose. The addition of 8-bromo-cGMP (8-Br-cGMP) or monobutyryl cGMP to the islets during a linear phase of glucose utilization resulted in concentration- and time-dependent increases in glucose utilization. Effects of the analogs of cGMP on glucose utilization were noted as early as 5 min after the onset of stimulation in the presence of 10 mM glucose. 8-Br-cGMP also increased the utilization of 1 mM glucose within 20 min. Stimulatory effects of 8-Br-cGMP were observed in the presence of cycloheximide or N-acetylglucosamine. Neither 8-bromo-cAMP (8-Br-cAMP) nor monobutyryl cAMP induced significant changes in glucose utilization at 1 or 10 mM glucose. In the presence of 3-isobutyl-1-methylxanthine (IBMX), 8-Br-cGMP, but not 8-Br-cAMP, induced a rapid change in glucose utilization. N-Methyl-N'-nitro-N-nitrosoguanidine, which activates guanylate cyclase, also stimulated glucose utilization in the presence of IBMX by 3-fold. IBMX alone did not change glucose utilization. In contrast, 8-Br-5'-GMP reduced glucose utilization, whereas 8-bromoinosine 3',5'-monophosphate and 8-bromoguanosine did not change glucose utilization. Sodium bromide did not affect glucose utilization. Glucose-stimulated insulin release was potentiated by 8-Br-cGMP, whereas insulin release from islets incubated in the absence of glucose or the presence of glyceraldehyde or 2-ketoisocaproic acid was not altered by 8-Br-cGMP. Thus, glucose utilization in pancreatic islets is modulated by cGMP, and the secretory response to 8-Br-cGMP is glucose dependent.
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PMID:Effects of guanosine 3',5'-monophosphate on glucose utilization in isolated islets of Langerhans. 243 25

The roles of cyclic AMP and cyclic GMP in the control of normal cell growth and the pathogenesis of malignant transformation remain uncertain. Several chemical carcinogens rapidly activate the guanylate cyclase-cyclic GMP systems of human and other mammalian tissues, and probably do so through unique free radical or redox reactions not involved in the physiologic regulation of celluar cyclic GMP. Short-term studies in lymphocytes and colonic mucosa with the N-nitroso carcinogen MNNG have failed to demonstrate a direct relationship between the acute increases in cyclic GMP induced by this agent and stimulation of DNA synthesis. Nevertheless, a role for this early cyclic GMP response in the complex processes by which MNNG and other carcinogenic stimuli of cyclic GMP initiate cell transformation is not excluded by these observations. Alternatively, increases in cyclic GMP could be part of the cellular response to injury and linked to the detoxification of chemical carcinogens or other noxious stimuli, rather than to a direct stimulation of cell proliferation. Resolution of these questions clearly awaits a better understanding of the normal cellular actions of cyclic GMP.
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PMID:Cyclic nucleotides in carcinogenesis: activation of the guanylate cyclase-cyclic GMP system by chemical carcinogens. 610 15