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)

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

Leukotriene C4 (LTC4) enhanced the association of mouse peritoneal macrophages (MPM) with Trypanosoma cruzi, increasing the proportion of MPM associating with parasites and the number of trypanosomes per MPM. LTC4 affected both cells since pretreatment of either one increased the association. LTC4 also enhanced MPM uptake of killed T. cruzi or latex beads, denoting stimulation of phagocytosis. However, since LTC4 pretreatment of rat heart myoblasts--nonphagocytic cells--also increased the association, host cell membrane alterations induced by LTC4 may also facilitate parasite invasion. Inhibition of MPM guanylate cyclase abrogated the LTC4 effect, suggesting a role for elevated levels of cyclic GMP. LTC4 also increased the rate of intracellular parasite killing by MPM. These results suggest that LTC4, occurring in inflammation such as develops in T. cruzi infection, regulates parasite clearance by MPM by increasing uptake and intracellular destruction.
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PMID:Effects of leukotriene C4 on macrophage association with and intracellular fate of Trypanosoma cruzi. 285 21

The goal of this study was to determine the role of nitric oxide in alterations in macromolecular transport of the hamster cheek pouch in vivo in response to leukotriene C4. We used intravital fluorescent microscopy to examine the transport of macromolecules across the hamster cheek pouch in response to leukotriene C4 before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextran; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increase in the number of venular leaky sites and clearance of FITC-dextran-70K. Superfusion of L-NMMA (1.0 microM) significantly decreased leukotriene C4-induced increases in venular leaky sites and clearance of FITC-dextran-70K. In addition, superfusion of LY-83583 (10 microM) significantly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of NG-monomethyl-D-arginine (D-NMMA; 1.0 microM), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-20 mg/kg iv) did not significantly alter leukotriene C4-induced increases in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play an important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.
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PMID:Role of nitric oxide in leukotriene C4-induced increases in microvascular transport. 834 60