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)

1. An epithelium-derived inhibitory factor (EpDIF) released by guinea-pig tracheal epithelium was evaluated in a co-axial bioassay system consisting of an epithelium-intact guinea-pig tracheal tube surrounding endothelium-denuded rat aortic strip. 2. Histamine and several muscarinic agonists induced concentration-dependent relaxation of phenylephrine-contracted rat aorta via the release of EpDIF. However, several other agonists did not induce the release of EpDIF from guinea-pig trachea. These included the nicotinic cholinoceptor agonists nicotine (25 microM), 1,1-dimethyl-4-phenylpiperazinium (DMPP) (25 microM), calcium ionophore A23187 (0.5 microM), bradykinin (0.05-0.5 microM), substance P (5 microM), platelet activating factor (PAF, 1-100 nM), the leukotrienes (LT) LTC4, LTD4 and LTE4 (0.1-10 nM) as well as hyperosmotic stimuli. 3. Prostaglandin E2 (PGE2) induced concentration-dependent contraction of endothelium-denuded rat aortic preparations, indicating that this prostanoid could not be EpDIF. Furthermore, relaxation to histamine and methacholine, mediated via EpDIF, was not significantly altered in the presence of phenidone (50 microM) the cyclo-oxygenase/lipoxygenase inhibitor with radical scavenging properties or the cytochrome P-450 inhibitors metyrapone (1 mM) and SKF 525A (25 microM). This suggests that EpDIF is neither a prostanoid nor a cytochrome P-450 metabolite of arachidonic acid. 4. The soluble guanylate cyclase inhibitor, methylene blue (50 microM), caused small but significant increases in the potencies of both histamine and methacholine in co-axial assemblies, indicating that EpDIF did not activate this enzyme and therefore was not NO or a related substance. The beta-adrenoceptor antagonist, (-)-propranolol (1 microM), and the PAF-receptor antagonist, WEB 2086 (50 microM), also failed to alter significantly EpDIF-modulated relaxations. These data suggest that EpDIF is neither a stimulant of fiadrenoceptors nor of PAF receptors. 5. The present study provides some evidence that this vascular smooth muscle-sensitive EpDIF may not be related to the putative EpDIF previously hypothesized to modulate directly spasmogen-induced airway smooth muscle tone.
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PMID:Pharmacological evaluation of a guinea-pig tracheal epithelium-derived inhibitory factor (EpDIF). 239 Jun 83

PAF elicits a rapid, concentration-dependent elevation of platelet cytosolic free calcium ([Caf]), measured by quin2. Elevation of [Caf] is transient, and the rate of reversal increases with agonist concentration. Adenylate cyclase stimulants (PGI2, PGD2) and 8-bromo cAMP; a guanylate cyclase stimulant (sodium nitroprusside) and 8-bromo cGMP; and a protein kinase C stimulant (phorbol myristate acetate) block the elevation of [Caf] induced by PAF, and accelerate its reversal. These results suggest that cAMP, cGMP and 1,2-diacylglycerol (DAG) could act as second messengers to regulate [Caf] in platelets. As PAF is known to stimulate platelet phosphoinositide hydrolysis (ergo DAG formation) but fails to elevate platelet cAMP or cGMP, it is proposed that DAG, via activation of protein kinase C, may act as an endogenous modulator of platelet [Caf]: an action that contributes to the role of DAG as a bi-directional regulator of platelet reactivity.
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PMID:Regulation of platelet cytosolic free calcium by cyclic nucleotides and protein kinase C. 299 27

Yersinia pestis toxin (II fraction by E. Baker) inhibited aggregation of human platelets as well as elevation of Ca2+, induced by different agonists ADP, PAF, thrombin. Agonist-induced Ca2+ mobilization and Ca2+ influx were dose-dependently inhibited by the toxin. The effect was rapid, developing during the first minute of incubation with the toxin. In contrast to murine lethal protein the platelet inhibitory activity was thermostable. The action of thermostable factor on platelets was accompanied by elevation of cellular cGMP level. This factor of Y. pestis activated guanylate cyclase in human platelets.
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PMID:[Features of regulatory system function in platelets under the effect of plague toxin]. 761 91

The study shows that endothelial cells from human umbilical veins have a soluble guanylate cyclase which can be activated by sodium nitroprusside (SNP), SIN-1 (3-morpholinosydnonimine) and S35b (4-methyl-3-phenylsulfonylfuroxan). Cells which were pretreated with these compounds showed an inhibition of thrombin-induced arachidonic acid release, PGI2 formation, PAF synthesis and PMNL adhesion. Endothelial guanylate cyclase can also be activated by nitric oxide (NO) which is generated in endothelial cells upon stimulation with thrombin or ionomycin. It is suggested that endogenously produced NO might control cell activation and endothelial function through a cGMP-dependent mechanism.
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PMID:Activation of endothelial guanylate cyclase inhibits cellular reactivity. 771 76

The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 microM) were used to induce release of t-PA and vWF. The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP. The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP. None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.
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PMID:The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor. 809 63

The action of sodium nitroprusside, an activator of guanylate cyclase, on rabbit platelets stimulated with PAF-acether, was studied singly or in combination with verapamil. Not only did sodium nitroprusside in the range 10(-6) to 10(-4) M inhibit PAF-acether induced aggregation, but it also brought about desaggregation of previously aggregated platelets, as also did verapamil. The results were compared with those obtained with PGE(1), when used alone and in combination with verapamil. Morphological studies were carried out on control and aggregated platelets, and on platelets treated with verapamil either to inhibit aggregation or to bring about desaggregation. The platelets that had been desaggregated by verapamil were discoid in shape, had very few pseudopodia and exhibited a near normal internal morphology, except that the open canalicular system was swollen and contained an electron dense material resembling the contents of the alpha granules. The morphology of platelets desaggregated by PGE(1) was similar to that of platelets desaggregated by verapamil, including a swollen canalicular system containing electron dense material.
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PMID:Desaggregation by Verapamil, Sodium Nitroprusside and PGE(1), of Rabbit Platelets Aggregated by PAF-acether. A Morphological and Biochemical Study. 2104 60